Sensor chip, biosensor system, method for measuring temperature of biological sample, method for measuring temperature of blood sample, and method for measuring concentration of analyte in blood sample

ABSTRACT

A sensor chip ( 200 ) includes a measuring unit ( 41 ) and a measuring unit ( 42 ). The measuring unit ( 41 ) includes an electrode system (temperature electrodes) having a portion ( 31 ) of an electrode ( 11 ) and a portion ( 32 ) of an electrode ( 12 ), and a portion of a capillary ( 40 ) containing the portion ( 31 ) and the portion ( 32 ). The measuring unit ( 42 ) includes an electrode system (analysis electrodes) having a portion ( 33 ) of a sensor electrode ( 13 ) and a portion ( 34 ) of an electrode ( 14 ), and a portion of a capillary ( 40 ) containing the portion ( 33 ) and the portion ( 34 ) in addition to a reaction reagent layer ( 20 ). Data (a) related to the temperature of the blood sample is acquired based on the dimension of a current flowing through the temperature electrodes, and data (b) related to a concentration of an analyte in the blood sample is acquired based on the dimension of a current flowing through the analysis electrodes.

TECHNICAL FIELD

The present invention relates to a sensor chip, a biosensor system, amethod for measuring temperature for a biological sample, a method formeasuring temperature for a blood sample, and a method for measuring aconcentration of an analyte in a blood sample.

BACKGROUND ART

A portable biosensor system provided with a measuring device having acalculating unit and a sensor chip detachable from the measuring deviceis used for measuring an analyte concentration, for example a bloodglucose concentration (blood glucose value) in a blood sample. Theanalyte concentration is calculated by an optical method or anelectrochemical method based on an amount of a reductant or an oxidantproduced by an oxygen cycling reaction mediated by an oxidoreductasethat uses the analyte as a substrate. The speed of the oxygen cyclingreaction depends on the temperature that promotes the reaction (reactiontemperature). As a result, the concentration of the analyte ispreferably corrected with reference to the reaction temperature.

The reaction temperature for example is measured by a temperature sensordisposed in the measuring device (Patent Literature 1). However, in thebiosensor system according to Patent Literature 1, the inner portiontemperature of the measuring device is measured, and therefore themeasured reaction temperature does not accurately reflect thetemperature of the blood sample. As a result, an error may result in themeasurement of the analyte concentration.

Patent Literature 2-4 disclose a biosensor system for improving themeasurement accuracy of the reaction temperature. The biosensor systemin Patent Literature 2 and 3 includes a heat conduction member inproximity to the blood sample retention unit of the sensor chip, anddetects the temperature of the blood sample transmitted through the heatconduction member with a temperature sensor disposed in the measuringdevice. Since the biosensor system in Patent Literature 2 and 3 includesa resin plate disposed between the heat conduction member and the bloodsample retention unit, the heat conduction member does not come intocontact with the blood sample. The biosensor system in Patent Literature4 includes a temperature sensor and a heat conduction member disposed ina mounting unit of the measuring device for mounting of the sensor chip,and therefore transmits the temperature of the blood sample to thetemperature sensor through the heat conduction member.

CITATION LIST Patent Literature

Patent Literature 1: Japanese Patent Application Laid-Open No.2003-156469

Patent Literature 2: Japanese Patent Application Laid-Open No.2001-235444

Patent Literature 3: Japanese Patent Application Laid-Open No.2003-42995

Patent Literature 4: Pamphlet of PCT International Application No.2003/062812

SUMMARY Technical Problem

When a user with a biosensor system moves into a location that has alarge temperature difference (for example, moves from an externallocation in summer or winter into a building), the measuring device willbe incapable of tracking the sharp variation in the environmentaltemperature, and for a certain period of time, will maintain a highertemperature or lower temperature than the environment of the currentlocation. For example, when moving the measuring device from a 40° C. ora 10° C. environment to a 25° C. environment, a period of approximately30 minutes may be required until the temperature of the measuring devicereaches 25° C. (Patent Literature 1).

It is difficult to completely eliminate the effect of the temperature ofthe measuring device when measuring the reaction temperature by atemperature sensor in a measuring device. Thus when there is a sharpchange in the temperature of the environment in which the sensor isused, an error will tend to be produced in the measurement of an analyteconcentration when using the biosensor system disclosed in PatentLiterature 2-4.

Since the temperature of the blood sample in the biosensor systemdisclosed in Patent Literature 2-4 is communicated by heat transferthrough the resin plate and the heat conduction member to thetemperature sensor, the measured reaction temperature does notaccurately reflect the temperature of the blood sample.

The present invention has the object of providing a biosensor system anda sensor chip for application to the biosensor system that measures atemperature of a blood sample and suppresses the production of ameasurement error resulting from the temperature of a use environment.Furthermore the present invention has the object of providing ameasurement method that improves the measurement accuracy of an analyteconcentration in a blood sample.

Solution to Problem

A sensor chip according to a first aspect of the present invention is asensor chip for measuring the temperature of a biological sample andincludes temperature electrodes having at least a working electrode andan counter electrode for measuring the temperature of the biologicalsample, and having a direct current voltage applied thereto, and acapillary configured to introduce the biological sample to thetemperature electrodes. The working electrode and/or the counterelectrode in the temperature electrodes are disposed to make contactwith the biological sample introduced into the capillary. The directcurrent voltage is set to reduce an effect of hematocrit on atemperature measurement result of hematocrit during application of thedirect current voltage.

In this sensor chip, a predetermined direct current voltage is appliedto the temperature electrodes so that the effect of hematocrit is lowduring measurement of the biological sample temperature by thetemperature electrodes.

In this manner, temperature measurement of a biological sample isenabled without reference to a hematocrit value in the biologicalsample. As a result, the temperature measurement accuracy for abiological sample can be improved, and the accuracy in relation tovarious types of corrections using the temperature of the biologicalsample can also be improved.

A sensor chip according to a second aspect of the present inventionincludes the sensor chip according to the first aspect, and the uptakeamount of the biological sample into the capillary is 5 μL or less, andthe application time of the direct current voltage to the temperatureelectrodes is 15 seconds or less.

A sensor chip according to a third aspect of the present inventionincludes the senor chip according to the first or the second aspect, andthe predetermined direct current voltage is within a range in which thesolvent of the biological sample is subjected to electrolysis.

A sensor chip according to a fourth aspect of the present inventionincludes the senor chip according to any one of the first to the thirdaspect, and is disposable.

A sensor chip according to a fifth aspect of the present invention is asensor chip for measuring the concentration of an analyte in a bloodsample, and includes temperature electrodes disposed to make contactwith the blood sample, and having at least a working electrode and ancounter electrode for measuring the temperature of the blood sample, anda concentration measuring unit configured to measure a feature relatedto a concentration of the analyte in the blood sample.

In this manner, direct measurement of the temperature of a blood sampleis enabled in contrast to a conventional sensor chip provided withtemperature electrodes that measure the heat transmitted through a resinplate, heat conduction member, or the like. As a result, the productionof a measurement error caused by the temperature of the use environmentcan be suppressed, and an improvement in the measurement accuracy of theanalyte concentration in a blood sample is enabled.

A sensor chip according to a sixth aspect of the present inventionincludes the sensor chip according to the fifth aspect, and theconcentration measuring unit is formed from analysis electrodesincluding at least a working electrode and an counter electrode.

A sensor chip according to a seventh aspect of the present inventionincludes the sensor chip according to the sixth aspect, and thetemperature electrodes and the analysis electrodes are providedseparately.

In this manner, accurate measurement of a concentration of an analyte ina blood sample is enabled.

A sensor chip according to an eighth aspect of the present inventionincludes the sensor chip according to the sixth or the seventh aspect,and further includes a sample introduction port and a capillaryconfigured to introduce a blood sample from the sample introduction portto the temperature electrodes and the analysis electrodes. Thetemperature electrodes are disposed at a position closer to the sampleintroduction port than the analysis electrodes.

A sensor chip according to a ninth aspect of the present inventionincludes the sensor chip according to any one of the fifth to the eighthaspect, and the temperature electrodes are disposed to not make contactwith at least one of the oxidoreductase or the electron mediator.

In this manner, the temperature of the blood sample can be accuratelymeasured.

A sensor chip according to a tenth aspect of the present inventionincludes the sensor chip according to any one of the fifth to the ninthaspect, and the concentration measuring unit further includes a reactionreagent that induces an oxidation-reduction reaction, and thetemperature electrodes are disposed to not make contact with thereaction reagent that induces the oxidation-reduction reaction.

In this manner, contact of the reaction reagent with the temperatureelectrodes can be avoided, and accurate measurement of the blood sampletemperature is enabled.

A sensor chip according to an eleventh aspect of the present inventionincludes the sensor chip according to any one of the fifth to the ninthaspect, and is disposed to not make contact with any reagent.

In this manner, contact of any reagent with the temperature electrodescan be avoided, and accurate measurement of the blood sample temperatureis enabled.

A sensor chip according to a twelfth aspect of the present inventionincludes the sensor chip according to the sixth aspect, and the workingelectrode of the temperature electrodes is common to at least either theworking electrode or the counter electrode of the analysis electrodes.

A sensor chip according to a thirteenth aspect of the present inventionincludes the sensor chip according to the sixth aspect, and the counterelectrode of the temperature electrodes is common to at least either theworking electrode or the counter electrode of the analysis electrodes.

A sensor chip according to a fourteenth aspect of the present inventionincludes the sensor chip according to any one of the sixth to the eighthaspect, and the concentration measuring unit includes at least oneelectrode in addition to the working electrode and the counterelectrode, and at least one of the electrodes of the concentrationmeasuring unit other than the working electrode and the counterelectrode is common to at least one of the working electrode and thecounter electrode of the temperature electrodes.

The electrodes included in the concentration measuring unit according tothe twelfth to the fourteenth aspects may be combined with at least oneof the working electrode and the counter electrode of the temperatureelectrodes.

The sensor chip according to the twelfth and the thirteenth aspects mayinclude a plurality of working electrodes and/or a plurality of counterelectrodes as analysis electrodes. At least one of the plurality ofworking electrodes and/or counter electrodes may be combined with theworking electrode and/or counter electrode of the temperatureelectrodes.

An example of an electrode other than a working electrode and counterelectrode according to the fourteenth aspect includes

a hematocrit measuring electrode;

a measuring electrode for an amount or concentration of a reducingsubstance;

a detection electrode for detecting the introduction of blood; and

a measuring electrode other than a electrode for measuring an amount orconcentration of a reducing substance, hematocrit, or glucoseconcentration.

A sensor chip according to a fifteenth aspect of the present inventionincludes the sensor chip according to the sixth aspect, and the surfacearea of the working electrode in the temperature electrodes is eitherthe same or smaller than the surface area of the counter electrode inthe temperature electrodes.

A sensor chip according to a sixteenth aspect of the present inventionincludes the sensor chip according to any one of the fifth to thefifteenth aspect, and at least hematocrit is included as a feature inrelation to the concentration of the analyte.

A sensor chip according to a seventeenth aspect of the present inventionincludes the sensor chip according to any one of the fifth to thesixteenth aspect, and at least a concentration or an amount of areducing substance is included as a feature in relation to theconcentration of the analyte.

A method for measuring a temperature of a biological sample according toan eighteenth aspect of the present invention measures a temperature ofa biological sample by a sensor chip including temperature electrodesformed from a working electrode and an counter electrode, and acapillary. The method includes an introduction step of introducing abiological sample by the capillary to the temperature electrodes, anapplication step of applying a direct current voltage to the temperatureelectrodes, and an adjustment step of adjusting the direct currentvoltage applied in the application step to a first voltage. The firstvoltage is set so that the effect of hematocrit on the temperaturemeasurement result during application of the first voltage to thetemperature electrodes is reduced.

This method enables temperature measurement of a biological samplewithout reference to a hematocrit value in the biological sample. As aresult, the accuracy of the temperature measurement of the biologicalsample can be increased, and the accuracy in relation to variouscorrections using the temperature of the biological sample can also beincreased.

A method for measuring a temperature according to a nineteenth aspect ofthe present invention includes the method for measuring a temperatureaccording to the eighteenth aspect, and a direct current voltage thatenables a reduction of the effect of hematocrit on the temperaturemeasurement result is measured and stored in advance, and the adjustmentstep adjusts to the first voltage based on the stored direct currentvoltage.

A method for measuring a temperature of a biological sample according toa twentieth aspect of the present invention includes the method fortemperature measurement of a biological sample according to theeighteenth or the nineteenth aspect, and the uptake amount of thebiological sample in the introduction step is 5 μL or less, and theapplication time of the direct current voltage in the application stepis 15 seconds or less.

A method for measuring a temperature of a blood sample according to atwenty first aspect of the present invention measures a temperature of ablood sample using a sensor chip including temperature electrodes formedfrom a working electrode and an counter electrode. The method includes astep of applying a voltage to the temperature electrodes in contact withthe blood sample, a step of acquiring data a related to the temperatureof the blood sample based on a dimension of a current flowing in theblood sample by application of the voltage, and a step of calculating atemperature t of the blood sample based on the data a.

A temperature t of the blood sample is calculated based on data arelated to the temperature of the blood sample that can be acquired byapplication of a voltage to the temperature electrodes in contact withthe blood sample.

In this manner, since the temperature t of the blood sample can becalculated based on data a related to the temperature of the bloodsample that can be accurately acquired, the production of a measurementerror caused by the temperature of the use environment can besuppressed.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty second aspect of the present invention includes astep of acquiring data a related to the temperature of the blood samplebased on the dimension of a current flowing in the blood sample byapplication of a voltage to the pair of electrodes in contact with theblood sample, a step of acquiring data b related to a concentration ofthe analyte based on the dimension of a current flowing in the bloodsample by a reaction mediated by an oxidoreductase that uses the analytein the blood sample as a substrate, and a step of measuring aconcentration that determines the analyte concentration in the bloodsample based on the data a and the data b.

Herein, the data a is acquired by directly measurement of thetemperature of the blood sample without interposing a resin plate or aheat conduction member, and the analyte concentration in the bloodsample is determined based on the data a related to the temperature ofthe blood sample and the data b related to the concentration of theanalyte.

In this manner, the measurement accuracy of the analyte concentration inthe blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty third aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of correcting the data b based on the data a.

In this manner, the measurement accuracy of the concentration of theanalyte in the blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty fourth aspect of the present invention includesthe method for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of calculating a concentration x of an analyte in ablood sample based on the data b, and a step of correcting theconcentration x based on the data a.

In this manner, the measurement accuracy of the concentration of theanalyte in the blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty fifth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of calculating a temperature t of the analyte inthe blood sample based on the data a, and a step of correcting the datab based on the temperature t.

In this manner, the measurement accuracy of the concentration of theanalyte in the blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty sixth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of calculating a temperature t of an analyte in ablood sample based on the data a, a step of calculating a concentrationx of the analyte in a blood sample based on the data b, and a step ofcorrecting the concentration x based on the temperature t.

In this manner, the measurement accuracy of the concentration of theanalyte in the blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty seventh aspect of the present invention includesthe method for measuring a concentration of an analyte in a blood sampleaccording to any one of the twenty second to the twenty sixth aspect,and the step of acquiring the data a is performed in advance of the stepof acquiring the data b.

In this manner, the temperature at the time of acquiring the data b canbe more accurately reflected.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty eighth aspect of the present invention includesthe method for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of acquiring data c related to the temperature ofthe blood sample based on the dimension of a current flowing in theblood sample by application of a predetermined voltage to the pair ofelectrodes in contact with the blood sample after acquisition of thedata b, and a step of calculating data d related to the temperature ofthe blood sample based on the data a and the data c, and a step ofcorrecting the data b based on the data d.

In this manner, the temperature at the time of acquiring the data b canbe more accurately reflected, and the analyte concentration measurementaccuracy for the blood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a twenty ninth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to the twenty second aspect, and the concentration measurementstep includes a step of calculating the temperature t of the bloodsample based on the data a, a step of calculating the concentration x ofthe analyte in the blood sample based on the data b, the step ofmeasuring an environmental temperature t1 on a periphery of the bloodsample, a step of comparing the difference between the temperature t andthe environmental temperature t1 with a temperature threshold Z, and astep of correcting the concentration x based on the temperature t whenthe relation |t−t1|≧Z is satisfied, and correcting the concentration xbased on the temperature t1 when the relation |t−t1|<Z is satisfied.

Herein, the concentration x of the analyte in the blood sample iscalculated based on the data b, and the temperature t of the bloodsample is calculated based on the data a. The environmental temperaturet1 in the periphery of the blood sample is measured. Then the differencebetween the temperature t and the environmental temperature t1 iscompared with a temperature threshold Z, and correction is performed asdescribed below.

When |t−t1|≧Z is satisfied, the concentration x is corrected based onthe temperature t

When |t−t1|<Z is satisfied, the concentration x is corrected based onthe temperature t1

In this manner, since the concentration x can be corrected using anappropriate temperature in response to an external temperatureenvironment, a measurement accuracy for the analyte concentration in theblood sample can be improved.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirtieth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to any one of the twenty second aspect to the twenty ninthaspect, and a temperature is contained in the data a related to thetemperature of the blood sample, and a glucose concentration iscontained in the data b related to the concentration of the analyte.

Herein, the temperature is included as a feature of the data acquired asdata a, and the glucose concentration is included as a feature of thedata acquired as the data b.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty first aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to the thirtieth aspect, and hematocrit is included in thedata b related to the concentration of the analyte.

Herein, hematocrit is included as a feature of the data acquired as thedata b.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty second aspect of the present invention includesthe method for measuring a concentration of an analyte in a blood sampleaccording to the thirtieth or thirty first aspect, and the concentrationor amount of the reducing substance is contained in the data b relatedto the concentration of the analyte.

Herein, the amount or concentration of the reducing substance isincluded as a feature of the data acquired as the data b.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty third aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to any one of the thirtieth to the thirty second aspect, andat least two features of the data included in the data a and the data bare measured at the same time.

Herein, when the data a and the data b are measured, at least twofeatures of the data are measured at the same time. For example, theconcentration or the amount of the reducing substance and the glucoseconcentration are measured at the same time.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty fourth aspect of the present invention includesthe method for measuring a concentration of an analyte in a blood sampleaccording to any one of the thirtieth to the thirty second aspect, andindependent measurement of the respective data included in the data aand the data b is executed.

Herein, when the data a and the data b are measured, two or morefeatures are not measured at the same time, but are measured separately.The order of measuring the features may be arbitrary.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty fifth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to any one of the thirtieth to the thirty second aspect, andthe measurement of the data contained in the data a and the data b isperformed in order of temperature, glucose concentration, concentrationor amount of the reducing substance, and hematocrit.

Herein, the order of measuring the data is specified. In this manner,effective results can be obtained with respect to speed, accuracy, andburden on the electrodes.

A method for measuring a concentration of an analyte in a blood sampleaccording to a thirty sixth aspect of the present invention includes themethod for measuring a concentration of an analyte in a blood sampleaccording to any one of the thirtieth to the thirty fifth aspect, andthe measurement of the data contained in the data a and the data b isperformed through independent electrodes.

Herein, when measuring the data contained in the data a and the data b,such measurement is performed by respectively independent electrodes.

A biosensor system according to a thirty seventh aspect of the presentinvention has the sensor chip according to any one of the first to theseventeenth aspects, and a measuring device including a control circuitapplying a voltage to the temperature electrodes of the sensor chip. Thebiosensor system measures a concentration of an analyte in a bloodsample. The biosensor system includes a voltage application unitconfigured to apply a voltage to the temperature electrodes inaccordance with the control circuit, a temperature measuring unitconfigured to acquire the data a related to the temperature of the bloodsample based on the dimension of a current flowing in the temperatureelectrodes in contact with the blood sample, an analyte measuring unitacquiring data b related to the concentration of the analyte based onthe dimension of a current flowing in the blood sample depending on areaction mediated by an oxidoreductase that uses the analyte in theblood sample as a substrate, and a concentration determination unitconfigured to determine an analyte concentration in the blood samplebased on the data a and the data b.

Herein, data a is acquired by direct measurement of the temperature ofthe blood sample and not through a resin plate or a heat conductionmember. The concentration determination unit determines the analyteconcentration in the blood sample based on the data a related to thetemperature of the blood sample and the data b related to the analyteconcentration.

In this manner, the production of a measurement error resulting from thetemperature of the use environment can be suppressed, and thereby themeasurement accuracy of the analyte concentration in the blood samplecan be improved.

A biosensor system according to the thirty eighth aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a firstanalyte correction unit configured to correct the data b based on thedata a.

Herein, the first analyte correction unit corrects the data b related tothe concentration of the analyte in the blood sample based on the data aacquired by direct measurement of the temperature of the blood sampleand not through a resin plate or a heat conduction member.

In this manner, the production of a measurement error resulting from thetemperature of the use environment can be suppressed, and thereby themeasurement accuracy of the analyte concentration in the blood samplecan be improved.

A biosensor system according to the thirty ninth aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a calculatingunit configured to calculate the concentration x of the analyte of theblood sample based on the data b, and a second analyte correction unitconfigured to correct the concentration x based on the data a.

Herein, the analyte correction unit calculates the concentration x ofthe analyte in the blood sample based on the data b, and then the secondanalyte correction unit corrects the concentration x based on the data aacquired by direct measurement of the temperature of the blood sample.

In this manner, the production of a measurement error resulting from thetemperature of the use environment can be suppressed, and thereby themeasurement accuracy of the analyte concentration in the blood samplecan be improved.

A biosensor system according to the fortieth aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a calculatingunit configured to calculate the temperature t of the blood sample basedon the data a, and a third analyte correction unit configured to correctthe data b based on the temperature t.

Herein, the calculating unit calculates the temperature t of the bloodsample based on the data a acquired by direct measurement of thetemperature of the blood sample, and then the third analyte correctionunit corrects the data b based on the temperature t.

In this manner, the production of a measurement error resulting from thetemperature of the use environment can be suppressed, and thereby themeasurement accuracy of the analyte concentration in the blood samplecan be improved.

A biosensor system according to the forty first aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a calculatingunit configured to calculate the temperature t of the blood sample basedon the data a, a calculating unit configured to calculate theconcentration x of the blood sample based on the data b, and a fourthanalyte correction unit configured to correct the concentration x basedon the temperature t.

Herein, the calculating unit calculates the temperature t of the bloodsample based on the data a acquired by direct measurement of thetemperature of the blood sample, and calculates the concentration x ofthe analyte in the blood sample based on the data b, and then the fourthanalyte correction unit corrects the concentration x based on thetemperature t.

In this manner, the production of a measurement error resulting from thetemperature of the use environment can be suppressed, and thereby themeasurement accuracy of the analyte concentration in the blood samplecan be improved.

A biosensor system according to the forty second aspect of the presentinvention includes the biosensor system according to any one of thethirty seventh aspect to the forty first aspect, and after acquisitionof the data a related to the temperature of the sample by thetemperature measuring unit, the data b related to the concentration ofthe analyte is acquired by the analyte measuring unit.

In this manner, the temperature when acquiring the data b can be moreaccurately reflected.

A biosensor system according to a forty third aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a temperaturemeasuring unit configured to acquire data c related to the temperatureof the blood sample based on the dimension of a current flowing in theblood sample by application of a predetermined voltage to the pair ofelectrodes in contact with the blood sample after acquisition of thedata b, a computing unit configured to calculate data d related to thetemperature of the blood sample based on data a and the data c, and acalculating unit configured to calculate the concentration x of theanalyte corrected in response to the temperature of the blood samplebased on the data d.

In this manner, after acquiring the data b, data c related to thetemperature of the blood sample is acquired by the same acquisitionmethod as the data a, and the computing unit calculates the data drelated to the temperature of the blood sample based on the data a andthe data c. Then the calculating unit corrects the concentration x basedon the data d.

In this manner, the temperature at the time of acquisition of the data bcan be more accurately reflected, and the measurement accuracy of theanalyte concentration in the blood sample can be improved.

A biosensor system according to a forty fourth aspect of the presentinvention includes the biosensor system according to the thirty seventhaspect, and the concentration determination unit includes a temperaturecalculating unit configured to calculate the temperature t of the bloodsample based on the data a, a concentration calculating unit configuredto calculate the concentration x of the analyte in the blood samplebased on the data b, an environmental temperature measuring unitconfigured to measure an environmental temperature t1 in a periphery ofthe blood sample, a comparison unit configured to compare the differencebetween the temperature t and the environmental temperature t1 with atemperature threshold Z, and a correction unit configured to correct theconcentration x based on the temperature t when the relation |t−t1|≧Z issatisfied, and correcting the concentration x based on the temperaturet1 when the relation |t−t1|<Z is satisfied.

Herein, the concentration x of the analyte in the blood sample iscalculated based on the data b, and the temperature of the blood sampleis calculated based on the data a. The environmental temperature t1 inthe periphery of the blood sample is measured. Then the differencebetween the temperature t and the environmental temperature t1 iscompared with a temperature threshold Z, and correction is performed asdescribed below.

When |t−t1|≧Z is satisfied, the concentration x is corrected based onthe temperature t

When |t−t1|<Z is satisfied, the concentration x is corrected based onthe temperature t1

In this manner, since the concentration x can be corrected using anappropriate temperature in response to an external temperatureenvironment, a measurement accuracy for the analyte concentration in theblood sample can be improved.

A biosensor system according to a forty fifth aspect of the presentinvention includes the biosensor system according to the any one of thethirty seventh aspect to the forty fourth aspect, and a temperature iscontained in the data a related to the temperature of the blood sample,and a glucose concentration is contained in the data b related to theconcentration of the analyte.

Herein, the temperature is included as a feature of the data acquired asdata a, and the glucose concentration is included as a feature of thedata acquired as the data b.

A biosensor system according to a forty sixth aspect of the presentinvention includes the biosensor system according to the forty fifthaspect, and hematocrit is included in the data b related to the analyteconcentration.

Herein, hematocrit is included as a feature of the data acquired as thedata b.

A biosensor system according to a forty seventh aspect of the presentinvention includes the biosensor system according to the forty fifthaspect or forty sixth aspect, and the concentration or amount of thereducing substance is contained in the data b related to theconcentration of the analyte.

Herein, the amount or concentration of the reducing substance isincluded as a feature of the data acquired as the data b.

A biosensor system according to a forty eighth aspect of the presentinvention includes the biosensor system according to the any one of theforty fifth to the forty seventh aspect, and further includes a sequencecontrol unit configured to control the control circuit so that at leasttwo features of the data included in the data a and the data b aremeasured at the same time.

Herein, when the data a and the data b are measured, the sequencecontrol unit controls the control circuit so that at least two featuresof the data are measured at the same time. For example, the sequencecontrol unit controls the control circuit so that the concentration orthe amount of the reducing substance and the glucose concentration aremeasured at the same time.

A biosensor system according to a forty ninth aspect of the presentinvention includes the biosensor system according to the any one of theforty fifth to the forty seventh aspect, and further includes a sequencecontrol unit configured to control the control circuit so thatindependent measurement of the respective data included in the data aand the data b is executed.

Herein, when the data a and the data b are measured, the sequencecontrol unit controls the control circuit so that two or more featuresof the data are not measured at the same time, but are measuredseparately. The order of measuring the features may be arbitrary.

A biosensor system according to a fiftieth aspect of the presentinvention includes the biosensor system according to the any one of theforty fifth to the forty seventh aspect, and further includes a sequencecontrol unit configured to control the control circuit so that themeasurement of the data contained in the data a and the data b isperformed in order of temperature, glucose concentration, concentrationor amount of the reducing substance, or hematocrit.

Herein, the order of measuring the data is specified. In this manner,effective results can be obtained with respect to speed, accuracy, andburden on the electrodes.

A biosensor system according to a fifty first aspect of the presentinvention includes the biosensor system according to the any one of theforty fifth to the fiftieth aspect, and further includes an electrodeselection unit configured to control the control circuit so that themeasurement of the data contained in the data a and the data b isperformed through independent electrodes.

Herein, when measuring the data contained in the data a and the data b,the electrode selection unit controls the control circuit so that suchmeasurement is performed by respectively independent electrodes.

Advantageous Effects

According to the sensor chip, the biosensor system, the method formeasuring a temperature of a blood sample, and a method for measuring aconcentration of an analyte in a blood sample according to the presentinvention, the production of a measurement error resulting from thetemperature of a use environment is suppressed, and improvement of themeasurement accuracy of an analyte concentration in a blood sample isenabled.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a perspective view of a biosensor system according to a firstembodiment of the present invention.

FIG. 2 is a partial perspective view of a biosensor chip according tothe first embodiment of the present invention.

FIG. 3 is a through-view plan view of a biosensor chip according to thefirst embodiment of the present invention.

FIG. 4 is a circuit diagram in a biosensor system according to the firstembodiment of the present invention.

FIG. 5 is a flowchart illustrating a method for measuring an analyteconcentration in a blood sample in the biosensor system according to thefirst embodiment of the present invention.

FIGS. 6( a) and 6(b) is a flowchart illustrating a method for measuringan analyte concentration in a blood sample in the biosensor system and acircuit diagram in a biosensor system according to another embodiment ofthe present invention.

FIGS. 7( a) and 7(b) is a flowchart illustrating a method for measuringan analyte concentration in a blood sample in the biosensor system, anda circuit diagram in a biosensor system according to another embodimentof the present invention.

FIGS. 8( a), 8(b) and 8(c) are graphs illustrating the variationcharacteristics of a current obtained by use of the biosensor chipaccording to the first embodiment of the present invention.

FIG. 9 is a partial perspective view of a sensor chip according to thefirst embodiment of the present invention.

FIG. 10 is a through-view plan view of a sensor chip according to thefirst embodiment of the present invention.

FIGS. 11( a), 11(b) and 11(c) are graphs illustrating the currentcharacteristics of a current corresponding to FIG. 8 according toWorking Example 1.

FIG. 12 is a graph illustrating the current characteristics obtained inrelation to a predetermined temperature according to Working Example 1.

FIGS. 13( a), 13(b), and 13(c) are graphs illustrating the currentcharacteristics obtained in relation to a predetermined applied voltageand a predetermined hematocrit value when the temperature in WorkingExample 7 is 4 degrees.

FIGS. 14( a), 14(b), and 14(c) are graphs illustrating the currentcharacteristics obtained in relation to a predetermined applied voltageand a predetermined hematocrit value when the temperature in WorkingExample 7 is 13 degrees.

FIGS. 15( a), 15(b), and 15(c) are graphs illustrating the currentcharacteristics obtained in relation to a predetermined applied voltageand a predetermined hematocrit value when the temperature in WorkingExample 7 is 21 degrees.

FIGS. 16( a), 16(b), and 16(c) are graphs illustrating the currentcharacteristics obtained in relation to a predetermined applied voltageand a predetermined hematocrit value when the temperature in WorkingExample 7 is 30 degrees.

FIGS. 17( a), 17(b), and 17(c) are graphs illustrating the currentcharacteristics obtained in relation to a predetermined applied voltageand a predetermined hematocrit value when the temperature in WorkingExample 7 is 38 degrees.

FIG. 18 is a graph illustrating the relationship with a current valueobtained in relation to a predetermined temperature in Working Example10.

FIG. 19 is a perspective view illustrating the inter-electrode distancein the sensor chip according to Working Example 11.

FIG. 20( a)-20D are graphs illustrating a response current value byhematocrit, and by inter-electrode distance when the blood sample is 11°C. in Working Example 11.

FIG. 21( a)-21(d) are graphs illustrating a response current value byhematocrit, and by inter-electrode distance when the blood sample is 21°C. in Working Example 11.

FIG. 22( a)-22(d) are graphs illustrating a response current value byhematocrit, and by inter-electrode distance when the blood sample is 30°C. in Working Example 11.

FIGS. 23( a) and 23(b) is a perspective view illustrating a sensor chipaccording to Working Example 12.

FIGS. 24( a) and 24(b) are graphs illustrating a response current valueby hematocrit, and by electrode shape when the blood sample is 11° C. inWorking Example 12.

FIGS. 25( a) and 25(b) are graphs illustrating a response current valueby hematocrit, and by electrode shape when the blood sample is 21° C. inWorking Example 12.

FIGS. 26( a) and 26(b) are graphs illustrating a response current valueby hematocrit, and by electrode shape when the blood sample is 30° C. inWorking Example 12.

FIGS. 27( a) and 27(b) is a perspective view illustrating a sensor chipaccording to Working Example 13.

FIG. 28( a)-28(d) are graphs illustrating a response current value byhematocrit, and by lead width when the blood sample is 30° C. in WorkingExample 13.

FIG. 29 is a perspective view illustrating the capillary height in thesensor chip in Working Example 14.

FIGS. 30( a) and 30(b) are graphs illustrating a response current valueby hematocrit, and by capillary height when the blood sample is 11° C.in Working Example 14.

FIGS. 31( a) and 31(b) are graphs illustrating a response current valueby hematocrit, and by capillary height when the blood sample is 21° C.in Working Example 14.

FIGS. 32( a) and 32(b) are graphs illustrating a response current valueby hematocrit, and by capillary height when the blood sample is 30° C.in Working Example 14.

FIGS. 33( a) and 33(b) are graphs illustrating a response current valueby palladium resistance when the blood sample is 4° C. in WorkingExample 15.

FIGS. 34( a) and 34(b) are graphs illustrating a response current valueby palladium resistance when the blood sample is 13° C. in WorkingExample 15.

FIGS. 35( a) and 35(b) are graphs illustrating a response current valueby palladium resistance when the blood sample is 21° C. in WorkingExample 15.

FIGS. 36( a) and 36(b) are graphs illustrating a response current valueby palladium resistance when the blood sample is 30° C. in WorkingExample 15.

FIGS. 37( a) and 37(b) are graphs illustrating a response current valueby palladium resistance when the blood sample is 38° C. in WorkingExample 15.

FIG. 38 is a graph illustrating response current value by glucoseconcentration when the blood sample is 24° C. in Working Example 15.

FIG. 39 is a graph illustrating response current value by ascorbic acidconcentration when the blood sample is 24° C. in Working Example 17.

FIG. 40 is a graph illustrating response current value by temperaturewhen the blood sample is introduced in an environment of 24° C. inWorking Example 18.

FIG. 41 is a perspective view illustrating the upward orientation anddownward orientation of the sensor chip according to Working Example 19.

FIG. 42 is a graph illustrating a response current value when blood isattached in an upward orientation and a downward orientation in anenvironment of 24° C. according to Working Example 19.

FIG. 43 is a graph illustrating a response current value when a distalend portion of the sensor chip is held between the fingers and not heldbetween the fingers in an environment of 24° C. according to WorkingExample 20.

FIG. 44 illustrates a measurement sequence in Working Example 21.

FIG. 45( a) is a graph illustrating a response current value for glucosemeasured in Working Example 21, and FIG. 45( b) is a graph illustratinga response current value for temperature and Hct measured in WorkingExample 21.

FIG. 46( a) is a graph illustrating a response current value fortemperature measurement in Working Example 21, and FIG. 45( b) is agraph illustrating a response current value by temperature whentemperature is measured in Working Example 21.

FIG. 47 illustrates another measurement sequence in Working Example 21.

FIG. 48( a) and FIG. 48( b) is a flowchart illustrates a measurementmethod for analyte concentration in a blood sample in a biosensor systemaccording to a first modified example according to the presentinvention.

FIG. 49( a) and FIG. 49( b) is a flowchart illustrates a measurementmethod for analyte concentration in a blood sample in a biosensor systemaccording to the first modified example according to the presentinvention.

FIG. 50( a) and FIG. 50( b) is a circuit diagram for a biosensor systemaccording to the first modified example according to the presentinvention.

FIG. 51( a) and FIG. 51( b) is a circuit diagram for a biosensor systemaccording to the first modified example according to the presentinvention.

FIG. 52 is a circuit diagram for a biosensor system according to asecond modified example according to the present invention.

FIG. 53 is a circuit diagram for a biosensor system according to anembodiment of the present invention.

DESCRIPTION OF EMBODIMENTS

The biosensor system according to the present invention acquires thetemperature of the analyte from the blood sample by a measuring unitdisposed in the sensor chip.

FIG. 1 illustrates an example of a biosensor system according to thepresent invention. The biosensor system 100 includes a rectangularparallelepiped measuring device 101 and a sensor chip 200. A mountingport 102 configured as a rectangular hole is formed in a side wallsurface of the measuring device 101. The sensor chip 200 is connected tothe measuring device 101 that is detachably attached to the mountingport 102. The display unit 103 that displays the measurement results isdisposed in a substantially central portion of one major surface of themeasuring device 101.

FIG. 2 is a partial perspective view of the sensor chip 200. FIG. 3 is aplan view thereof. In the sensor chip 200, a cover 203 is disposed on aninsulating plate 201 through a spacer 202 that forms a rectangular notch204, and leaves one end portion of the insulating plate 201 (the rightend in FIG. 2).

Each member 201, 202, 203 is integrated for example by adhesion orthermal welding. After integration of each of the members, the notch 204of the spacer 202 functions as a capillary 40 that retains the bloodsample. The capillary 40 has an elongated shape along the long side ofthe sensor chip 200, and communicates with an outer portion on one endportion of the spacer 202 (the left end portion in FIG. 2 and FIG. 3).In other words, the capillary 40 communicates with the blood sampleintroduction port 17 that opens onto an outer portion of the sensor chip200. The cover 203 includes a discharge port 16 in proximity to theopposite end to the side near the blood sample introduction port 17 inthe capillary 40. In this manner, the blood sample is easily aspiratedby capillary action from the blood sample introduction port 17 into aninner portion of the capillary 40.

Respective portions (portions 31, 32, 33, 34, 35) of the electrodes(voltage application portion) 11, 12, 13, 14, 15 are disposed on aninsulating plate 201 to face the capillary 40. The portion 31 of theelectrode 11 and the portion 32 of the electrode 12 are disposed at aposition in closer proximity to the blood sample introduction port 17than the portion 33 of the electrode 13 and the portion 34 of theelectrode 14.

A reaction reagent layer 20 is formed on the insulating plate 201 tocover the whole of the portion 33 of the electrode 13 and to partiallycover the portion 34 of the electrode 14 and the portion 35 of theelectrode 15. The reaction reagent layer 20 includes an oxidoreductasethat uses the analyte in the blood sample as a substrate, and anelectron mediator.

The reaction reagent layer 20 is formed at a position separated from theportion 31 of the electrode 11 and the portion 32 of the electrode 12.It is preferred that a reagent including an oxidoreductase or anelectron mediator is not disposed on the portion 31 of the electrode 11and the portion 32 of the electrode 12, and more preferably no reagentis disposed.

In an opposite configuration to the above, when the portion 33 of theelectrode 13 and the portion 34 of the electrode 14 are disposed at aposition in closer proximity to the blood sample introduction port 17than the portion 31 of the electrode 11 and the portion 32 of theelectrode 12, if the blood sample is introduced from the blood sampleintroduction port 17, the sample may reach the portion 33 of theelectrode 13 and the portion 34 of the electrode 14 due to flow in thereaction reagent layer 20 on the portion 33 of the electrode 13 and theportion 34 of the electrode 14. Therefore, this configuration should beavoided.

The sensor chip 200 includes a measuring unit 41 (measuring unit A). Themeasuring unit A is configured from an electrode system (temperatureelectrodes) formed by the portion 31 of the electrode 11 and the portion32 of the electrode 12, and a space in a portion of the capillary 40that contains the portion 31 and the portion 32.

The sensor chip 200 includes a measuring unit 42 (measuring unit B). Themeasuring unit B is configured from an electrode system (analysiselectrodes) formed by the portion 33 of the electrode 13 and the portion34 of the electrode 14, and a space in a portion of the capillary 40that contains the reaction reagent layer 20 in addition to the portion33 and the portion 34.

In the temperature electrodes of the measuring unit A, the electrode 11functions as a working electrode and the electrode 12 functions as ancounter electrode. In the analysis electrodes of the measuring unit B,the electrode 13 functions as a working electrode and the electrode 14functions as an counter electrode.

The measuring unit A (temperature measuring unit) acquires the data arelated to the temperature of the blood sample based on the amount ofcurrent flowing in the temperature electrodes. The substance thatexhibits an electrochemical reaction on the temperature electrodes ismainly a component of the blood sample, or may be water, or may be ablood-cell component such as red blood cells or white blood cells.

The measuring unit B (analyte measuring unit) acquires the data brelated to the concentration of the analyte in the blood sample based onthe amount of current flowing in the analysis electrodes. The substancethat exhibits an electrochemical reaction on the analysis electrodes ismainly an electron mediator that exchanges electrons with theoxidoreductase. The data b acquired in the measuring unit B is correctedbased on the temperature using the data a. The concentration of theanalyte is calculated using the data b after correction.

One or both of the portion 33 of the electrode 13 and the portion 34 ofthe electrode 14 may function as one or both of the portion 31 of theelectrode 11 and a portion 32 of the electrode 12. However it ispreferred that these electrodes are provided separately.

The portion 35 of the electrode 15 is disposed in proximity to the innerend portion of the capillary 40, that is to say, in proximity to theopposite end to the end that communicates with the outer portion.Application of voltage between the electrode 15 and the electrode 13facilitates detection when the blood sample is introduced to an innerportion of the capillary 40. The voltage may be applied between theelectrode 14 and the electrode 15 in substitution for the electrode 13.

The electrodes 11, 12, 13, 14, 15 are connected with respective leads(not illustrated). One end of the lead is exposed to an outer portion ofthe sensor chip 200 on the end portion of the insulating plate 201 thatis not covered by the spacer 202 and the cover 203 to thereby enableapplication of a voltage between each electrode.

The analyte in the blood sample may be a substance other than a bloodcell, and for example includes glucose, albumin, lactic acid, bilirubin,and cholesterol. The oxidoreductase may be a substance that uses thetarget analyte as a substrate. The oxidoreductase may be exemplified byglucose oxidase, glucose dehydrogenase, lactate oxidase, lactatedehydrogenase, bilirubin oxidase, and cholesterol oxidase. The amount ofthe oxidoreductase in the reaction reagent layer is 0.01-100 units (U),preferably 0.05-10 U, and more preferably 0.1-5 U.

The reaction reagent layer 20 preferably contains an electron mediatorthat has a function of exchanging electrons produced by an oxidationreaction with an electrode, such as potassium ferricyanide,p-benzoquinone, p-benzoquinone derivatives, oxidized phenazinemethosulfate, methylene blue, ferricinium and ferricinium derivatives.The reaction reagent layer 20 may include a water soluble polymercompound to increase molding characteristics of the reaction reagentlayer. The water soluble polymer compound may be exemplified from atleast one selected from the group consisting of carboxymethyl celluloseand salts thereof, hydroxyethyl cellulose, hydroxypropylcellulose,methylcellulose, ethylcellulose, ethylhydroxyethyl cellulose,carboxymethyl cellulose and salts thereof, polyvinylalcohol,polyvinylpyrrolidone, polyamino acids such as polylysine,polystyrenesulfonic acid and salts thereof, gelatin and derivativesthereof, polyacrylic acid and salts thereof, polymethacrylate and saltsthereof, starch and derivatives thereof, maleic anhydride polymers andsalts thereof, and agarose gel and derivatives thereof.

The material of the insulating plate 201, the spacer 202 and the cover203 is exemplified by polyethylene terephthalate, polycarbonate,polyimide, polyethylene, polypropylene, polystyrene, polyvinyl chloride,polyoxymethylene, monomer-cast nylon, polybutylene terephthalate, resinssuch as methacrylate resin and ABS resin, and glass.

The electrodes 11, 12, 13, 14, and 15 for example are configured from aknown conductive material such as palladium, platinum, gold, silver,titanium, copper, nickel, and carbon.

FIG. 4 illustrates an example of a circuit configuration for measuringan analyte concentration in a blood sample in the biosensor system 100.The measuring device 101 includes a control circuit 300 that applies avoltage between at least two electrodes of the electrodes 11, 12, 13, 14and 15 in the sensor chip 200, and a display unit 400 that displays themeasurement result.

The control circuit 300 includes five connectors 301 a, 301 b, 301 c,301 d, 301 e, a switching circuit 302, a current/voltage conversioncircuit 303, an analog/digital (A/D) conversion circuit 304, a referencevoltage power source 305, and a computing unit 306. The control circuit300 enables switching of the potential applied to the electrodes toenable use of one electrode as a cathode or as an anode through theswitching circuit 302.

The computing unit (concentration determination unit) 306 includes aknown central processing unit (CPU) and a conversion table fordetermining an analyte concentration in a blood sample based on the dataa and the data b. The computing unit 306 uses a correction coefficientbased on the environmental temperature to correct the analyteconcentration by reference to the conversion table above. Morespecifically, after referring to the conversion table for preliminarymeasurement and provisionally calculating the analyte concentration, thecomputing unit 306 corrects the analyte concentration by reference to aconversion table for temperature correction.

As illustrated in FIG. 5, the measurement of the analyte concentrationin the blood sample using the biosensor system 100 for example isexecuted as described below.

Firstly, the CPU in the computing unit 306 commands the electrode 13 toconnect with the current/voltage conversion circuit 303 through theconnector 301 b and the electrode 15 to connect with the referencevoltage power source 305 through the connector 301 c.

Thereafter, the CPU commands the application of a predetermined voltageto both electrodes (step S1). For example, when the voltage is denotedby the electrode 15 as the positive electrode and the electrode 13 asthe negative electrode, the voltage is 0.01-2.0V, preferably 0.1-1.0V,and more preferably 0.2-0.5V. The voltage is applied from insertion ofthe sensor chip into the measuring device 101 until the introduction ofthe blood sample into an inner portion of the capillary 40. When theblood sample is introduced into the capillary 40 from the blood sampleintroduction port of the sensor chip 200, a current flows between theelectrode 15 and the electrode 13. The CPU detects that the capillary 40is filled with the blood sample by discrimination of an increase amountin the current per unit time during this period. The current value isconverted to a voltage value by the current/voltage conversion circuit303 and then is converted to a digital value by the A/D conversioncircuit 304 and and input to the CPU. The CPU detects that the bloodsample is introduced into the inner portion of the capillary based onthe digital value.

After introduction of the blood sample, for example, the analyte in theblood sample and oxygen, and oxygen and the electron mediator arereacted within a range of 0-60 seconds, preferably 0-15 seconds, andmore preferably 0-5 seconds.

Then, the data a is acquired in the following manner (step S2).

Firstly, the voltage switching circuit 302 is operated by command of theCPU, the electrode 11 is connected with the current/voltage conversioncircuit 303 through the connector 301 a, and the electrode 12 isconnected with the reference voltage power source 305 through theconnector 301 e. Then the CPU commands application of a predeterminedvoltage between the electrodes in the measuring unit A. As describedbelow, when the voltage is denoted using the electrode 11 as thepositive electrode and the electrode 12 as the negative electrode, thevoltage is in the range of 0.1-5.0V, preferably 1.0-3.0V, and morepreferably 1.5-2.5V. The voltage application time is in the range of0.1-30 seconds, preferably from 0.5-10 seconds, and more preferably 1-5seconds. A signal commanding acquisition of the data a is output fromthe control circuit to the measuring unit A, to thereby cause thecurrent/voltage conversion circuit 303 to convert the current amountbetween both electrodes resulting from application of the voltage to avoltage amount. Thereafter, the voltage amount is converted to a digitalvalue by the A/D conversion circuit 304, inputted to the CPU, and storedin the memory of the computing unit 306 as the data a.

Thereafter, the data b is acquired as described below (step S3).

Firstly, the voltage switching circuit 302 is operated by command of theCPU, the electrode 13 is connected with the current/voltage conversioncircuit 303 through the connector 301 b, and the electrode 14 isconnected with the reference voltage power source 305 through theconnector 301 d. Then, the CPU commands commencement of the measurementsequence in the measuring unit B. The voltage applied at this time isdenoted using the electrode 13 as the positive electrode and theelectrode 14 as the negative electrode, and is in the range of0.05-1.0V, preferably 0.1-0.8V, and more preferably 0.2-0.6V. Thevoltage application time is from 0.1-30 seconds, preferably from 0.1-15seconds, and more preferably 0.1-5 seconds. A signal commandingacquisition of the data b is output from the control circuit to themeasuring unit B, and thereby cause the current/voltage conversioncircuit 303 to convert the current amount flowing between bothelectrodes as a result of the voltage application to a voltage amount.Thereafter the voltage is converted to a digital value by the A/Dconversion circuit 304, inputted to the CPU, and stored in the memory ofthe computing unit 306 as data b. From the point of view of enhancingthe measurement speed of the analyte concentration, the control circuitpreferably applies the signal commanding acquisition of the data b tothe measuring unit B within a range of at least 0.5 seconds and lessthan 5 seconds from the time that the blood sample is introduced intothe capillary 40 of the sensor chip.

The data b may be acquired prior to acquisition of the data a. However,prior to acquisition of the data b, since a sufficient period isrequired for dissolution of the sample, oxygen reaction of the electronmediator with oxygen, and the like, the data b is preferably acquiredafter acquisition of the data a. Furthermore, the data b and the data amay be acquired simultaneously. However, since a voltage is appliedsimultaneously to two groups of electrode systems in one solutionsystem, there may be interference between the respective currents.Consequently, separate acquisition of the data a and acquisition of thedata b is preferred.

As illustrated in FIG. 6( a), the temperature when acquiring the data bis more accurately reflected in the temperature measurement results byrespectively acquiring data related to temperature of the blood samplebefore and after the acquisition of the data b. In other words, thebiosensor system 100 applies a predetermined voltage to both electrodes(step S101), acquires the data a related to the temperature of the bloodsample (step S102), and then acquires the data b related to theconcentration of the analyte in the blood sample (step S103).Thereafter, the data c related to the temperature of the blood sample isre-acquired (step S104). Then, the computing unit 306 calculates thedata d by calculation of the average of the data a and the data c (stepS105), and calculates the analyte concentration by correcting thetemperature in the data b using the data d (step S106). As illustratedin FIG. 6(b), the computing unit (concentration determination unit) 306(refer to FIG. 4) in the biosensor system 100 includes a temperaturemeasuring unit 307 that acquires the data c related to the temperatureof the blood sample based on the dimension of the current flowingthrough the temperature electrodes that is in contact with the bloodsample after acquisition of the data b, a computing unit 308 thatcalculate the data d related to the temperature of the blood samplebased on the data a and the data c, and a concentration calculating unit309 that uses the data d to calculate the concentration x of the analytethat is corrected in response to the temperature of the blood sample.

Then the computing unit 306 refers to the conversion table anddetermines the analyte concentration in the blood sample based on thedata a the data b (step S4). The determined analyte concentration isdisplayed on the display unit 400. If a temperature conversion table isprepared in relation to the data a, the computing unit 306 can calculatethe temperature of the blood sample, and can display the temperature onthe display unit 400. A computing program used in this determination maybe suitably designed in response to the data structure of the conversiontable. When numerical data displaying a complete correspondence with thedata a and the data b is not stated in the conversion table, thecomputing unit 306 may determine the analyte concentration using datastated in the conversion table and a known interpolation method usingdata that approximates the data a and the data b.

If required, use of the electrode 11 and the electrode 12 may be used asan electrode for temperature measurement applications and an electrodefor other analyte applications. The other analyte application forexample includes measurement of a hematocrit value in the blood sample,and measurement of a reducing substance such as ascorbic acid, uricacid, bilirubin, acetaminophen, and the like. A method of using theelectrode 11 or the electrode 12 as the working electrode (positiveelectrode), the electrode 13 or the electrode 14 as the counterelectrode (negative electrode) is known.

In the present invention, the voltage between the temperature electrodesin the measuring unit A is affected by the configuration of the sensorchip such as the electrode material or the electrode surface area, andtherefore it is necessary to determine an optimal applied voltage inadvance. The current amount acquired when applying a voltage thatdiverges from an optimal value is affected by the hematocrit value (Hctvalue) in the blood sample. An Hct value means a numerical valueexpressing the ratio of the content of blood cells in blood.

When the optimal voltage value is denoted as Vm, a voltage value higherthan the optimal voltage value is denoted as Vh, and a voltage valuelower than the optimal voltage value is denoted as Vl, the change in thecurrent amount expressed by (Vl<Vm<Vh) is illustrated in FIG. 8. When avoltage value Vl that is lower than the optimal voltage value isapplied, as illustrated in FIG. 8( a), the current amount increases asthe value Hct increases. Conversely, when the voltage value Vh is higherthan the optimal voltage value is applied, as illustrated in FIG. 8( c),the current amount increases as the Hct value decreases. When theoptimal voltage value Vm is used, as illustrated in FIG. 8( b), a fixedcurrent amount is exhibited irrespective of the Hct value. A conspicuousestrangement of the current amount resulting from the Hct value isexhibited under high temperature conditions and a high current amount.Therefore the upper limiting temperature in the temperature measurementregion is preferably determined in advance. The Vm range is 0.1-5.0 V,preferably 1.0-3.0 V, and more preferably 1.5-2.5 V.

In the present invention, the current amount flowing between thetemperature electrodes in the measuring unit A is affected by theelectrode surface area. A higher current amount is obtained when eitherof the surface area of a portion 31 of the electrode 11 (workingelectrode) and the surface area of a portion 32 of the electrode 12(counter electrode) is increased. However it is preferred to increasethe surface area of the portion 32 that is on the counter electrodeside. More specifically, the range of the proportion of the surface areaof the working area/the surface area of the counter electrode ispreferably 1-0.25.

Even when there is a rapid change in the environmental temperature ofthe sensor, the biosensor system according to the embodiment enableshighly accurate measurement of the analyte concentration. As a result,there is no necessity to provide an environmental temperature measuringunit such as a thermistor in the measuring device.

However, the state or configuration of the sensor may result in a lowaccuracy in relation to the current amount obtained by the measuringunit A. For example, in a sensor that has a small surface-area capillary40, although the capacity of the blood sample required for measurementmay be reduced, the surface area of the temperature electrodes in themeasuring unit A must be reduced. Therefore, the current amount obtainedin the measurement A is decreased, and as a result, it is predicted thatthe accuracy of the current amount obtained in the measuring unit A willbe reduced. In this case, as illustrated in the circuit configurationdiagram in FIG. 53, the environmental temperature measuring unit 315 maybe provided in the measuring device. The number of environmentaltemperature measuring units 315 may be only one, or may be two or more.When two or more environmental temperature measuring units 315 areprovided, respective environmental temperature measuring units 315guarantee a more accurate measurement result for the environmentaltemperature by mutually monitoring of accuracy.

Furthermore, when temperature data obtained by the measuring unit A inthe sensor is compared with the temperature data obtained from athermistor provided in the measuring device, temperature correction maybe executed and the respective temperature change can be monitored, anoptimal temperature can be selected, and used for temperature correct.Furthermore, a method may be used in which the temperature is correctedby reference to the difference between the temperature of the measuringunit A and the temperature of the thermistor, or a method in which aplurality of temperature differences is acquired, and an optimaltemperature correction value is selected. Of course, a method ofutilizing data for average values and not temperature differences may beexecuted.

In the biosensor system 100 illustrated in FIG. 53, the computing unit306 compares the temperature t acquired by the measuring unit A and thetemperature t1 acquired by the environmental temperature measuring unit315 in the measuring device (step S43), and uses the temperature tacquired by the measuring unit A only when there is an error between thetwo. That is to say, as illustrated in FIG. 7( a), the computing unit306 calculates the temperature t based on the data a (step S41). Thecomputing unit 306 calculates the concentration x based on the data b(step S42). The environmental temperature measuring unit 315 measuresthe environmental temperature t1 (step S43).

When there is no difference between the outer environmental temperatureand the blood sample temperature, the computing unit 306 uses thetemperature t1 (step S45) since the environmental temperature measuringunit 315 has a high measurement accuracy.

When there is a difference between the outer environmental temperatureand the blood sample temperature as a result of a sharp variation in thetemperature, the environmental temperature measuring unit 315 cannotadapt to the difference. Therefore, the temperature t acquired by themeasuring unit A is adopted (step S46). More specifically, thetemperature threshold Z is preset. The computing unit 306 is comparesthe value for |t−t1| with the temperature threshold Z (step S44). Whenthe value for |t−t1| is higher than or equal to the temperaturethreshold Z, the computing unit 306 corrects the concentration x basedon the temperature t (step S45). When smaller than the temperaturethreshold Z, the concentration x is corrected based on the environmentaltemperature t1 (step S46).

The range of the temperature threshold Z is determined in considerationof the accuracy of the environmental temperature measuring unit of themeasuring device and the accuracy of the measuring unit A in the sensorchip, and is in the range of 0.01-5.0° C., preferably 0.1-2.0° C., andmore preferably 0.2-1.0° C.

As illustrated in FIG. 7( b), the computing unit (concentrationdetermination unit) 306 in the biosensor system 100 (refer to FIG. 4 andFIG. 52) includes a temperature calculating unit 310 and a concentrationcalculating unit 311. The temperature calculating unit 310 calculatesthe temperature t of the blood sample based on the data a. Theconcentration calculating unit 311 calculates the concentration x of theanalyte of the blood sample based on the data b.

The measuring device includes an environmental temperature measuringunit 312, a comparison unit 313, and a correction unit 314. Theenvironmental temperature measuring unit 312 measures the peripheralenvironmental temperature t1 of the blood sample. The comparison unit313 compares the difference between the temperature t and theenvironmental temperature t1 with the temperature threshold value Z. Thecorrection unit 314 corrects the concentration x based on thetemperature t when the expression |t−t1|≧Z is satisfied, and correctsthe concentration x based on the environmental temperature t1 when theexpression |t−t1|<Z is satisfied.

WORKING EXAMPLES

The invention will be described in further detail below with referenceto the embodiments.

Working Example 1

A sensor chip 210 is prepared as illustrated in FIG. 9 and FIG. 10. Thecapillary is designed with a width of 1.2 mm, a length (depth) of 4.0mm, and a height of 0.15 mm. The insulating plate is formed frompolyethylene terephthalate. After palladium is deposited by vapordeposition onto the insulating plate, the respective electrodes wereformed by formation of a slit in the palladium layer with a laser sothat the surface area of the portion 31 of the electrode 11 is 0.12 mm²,and the portion 32 of the electrode 12 is 0.48 mm².

Three types of blood samples having Hct values respectively of 25%, 45%and 65% were prepared. The temperature of the blood sample was taken tobe 23° C. These blood samples were introduced into the capillary ofseparate sensor chips. Thereafter, the electrode 11 was used as theworking electrode (positive electrode) and the electrode 12 was used asthe counter electrode (negative electrode), and a voltage of 2.0V, 2.2V,or 2.4V was applied between the electrodes (temperature electrodes). Thecurrent flowing between the working electrode and the counter electrode(response current) due to application of the voltage is measured.

The measurement results are illustrated in the graphs in FIG. 11( a),FIG. 11( b), and FIG. 11( c).

When the applied voltage is 2.0V, as illustrated in FIG. 11( a), theresponse current increases as the Hct value increases. These resultscorrespond to FIG. 8( a).

As illustrated in FIG. 11( b), when the applied voltage is 2.2V, theresponse current is fixed irrespective of the Hct value. These resultscorrespond to FIG. 8( b).

As illustrated in FIG. 11( c), when the applied voltage is 2.4V, theresponse current increases as the Hct value decreases. These resultscorrespond to FIG. 8( c).

Next, an experiment using a blood sample with an Hct 45% at 4° C.-38° C.was performed. At each temperature, the blood sample was introduced intothe capillary of separate sensor chips. Thereafter, the electrode 11 wasused as the working electrode (positive electrode) and the electrode 12was used as the counter electrode (negative electrode), and the responsecurrent was measured when a voltage of 2.2V was applied between theelectrodes (temperature electrodes). The measurement results areillustrated in the graph in FIG. 12. As illustrated in FIG. 12, theresponse current increases as the temperature increases.

The results in FIG. 11 and FIG. 12 demonstrate that a blood sampletemperature can be detected by applying a large voltage of 2.2V betweenthe electrode 11 and the electrode 12 and thereby measuring the responsecurrent.

Working Example 2

The sensor chip having the configuration described in Working Example 1was used, and a blood sample at a temperature of 23° C. and an Hct valueof 45% was introduced into the capillary of the sensor chip. Thereafter,the electrode 11 was used as the working electrode (positive electrode)and the electrode 12 was used as the counter electrode (negativeelectrode), and the response current was measured when a voltage of 2.2Vwas applied between the electrodes (temperature electrodes). Table 1below illustrates the current value after three seconds from initiationof voltage application. The current value in Working Example 2 was 1.88μA.

TABLE 1 Electrode Surface Area (mm²) Working Counter Current ValueCurrent Increase Electrode electrode (μA) Rate (%) Working 0.12 0.481.88 — Example 2 Working 0.24 0.48 2.47 32 Example 3 Working 0.48 0.483.13 67 Example 4 Working 0.12 0.96 3.08 65 Example 5 Working 0.24 0.963.65 94 Example 6

Working Example 3

An electrode was formed so that the surface area of the portion 31 ofthe electrode 11 of the sensor chip is 0.24 mm², and the surface area ofthe portion 32 of the electrode 12 of the sensor chip is 0.48 mm². Otherconditions are the same as the sensor chip described in Working Example2. Table 1 below illustrates the current value after three seconds frominitiation of voltage application. The current value in Working Example3 was 2.47 μA. When compared with Working Example 2, the current valueexhibits a 32% increase. The surface area of the working electrode inthe sensor chip in Working Example 3 is twice as large when comparedwith Working Example 2.

Working Example 4

An electrode was formed so that the surface area of the portion 31 ofthe electrode 11 of the sensor chip is 0.48 mm², and the surface area ofthe portion 32 of the electrode 12 of the sensor chip is 0.48 mm². Otherconditions are the same as the sensor chip described in Working Example2. Table 1 below illustrates the current value after three seconds frominitiation of voltage application. The current value in Working Example4 was 3.13 μA. When compared with Working Example 2, the current valueexhibits a 67% increase. The surface area of the working electrode inthe sensor chip in Working Example 4 is four times as large whencompared with Working Example 2 and twice as large when compared withWorking Example 3. In other words, it is shown that the current valueincreases as the surface area of the working electrode increases.

Working Example 5

An electrode is formed so that the surface area of the portion 31 of theelectrode 11 of the sensor chip is 0.12 mm², and the surface area of theportion 32 of the electrode 12 of the sensor chip is 0.96 mm². Otherconditions are the same as the sensor chip described in Working Example2. Table 1 below illustrates the current value after three seconds frominitiation of voltage application. The current value in Working Example5 was 3.08 μA. When compared with Working Example 2, the current valueexhibits a 65% increase. The surface area of the working electrode inthe sensor chip in Working Example 5 is twice as large when comparedwith Working Example 2. In other words, it is shown that the currentvalue increases as the surface area of the counter electrode increases.When compared with Working Example 3, the increase rate in the currentvalue only reaches 32% under the condition that the surface area of theworking electrode is two times. Therefore a higher response value isobtained by increasing the surface of the counter electrode more thanthe working electrode.

Working Example 6

An electrode is formed so that the surface area of the portion 31 of theelectrode 11 of the sensor chip is 0.24 mm², and the surface area of theportion 32 of the electrode 12 of the sensor chip is 0.96 mm². Otherconditions are the same as the sensor chip described in Working Example2. Table 1 below illustrates the current value after three seconds frominitiation of voltage application. The current value in Working Example6 was 3.65 μA. When compared with Working Example 2, the current valueexhibits a 94% increase. The surface area of the working electrode andthe counter electrode in the sensor chip in Working Example 6 is twiceas large when compared with Working Example 2. In other words, thecurrent value is also increased in proportion to an increase in theelectrode surface area when the ratio of the electrode surface areas isthe same.

Working Example 7

A sensor chip as described in Working Example 1 is prepared. Fifteenthtypes of blood samples being combinations of three Hct valuesrespectively of 25%, 45% and 65% and five temperatures of 4° C., 13° C.,21° C., 30° C., and 38° C. were prepared.

These blood samples were introduced into the capillary of separatesensor chips. Next, the electrode 11 was used as the working electrode(positive electrode) and the electrode 12 was used as the counterelectrode (negative electrode), and a voltage of 2.1V, 2.15V, or 2.2Vwas applied between the electrodes (temperature electrodes) to therebymeasure the response current at that time.

FIG. 13 to FIG. 17 are graphs illustrating the response current atrespective temperature conditions and applied voltages. The temperatureconditions and the applied voltage conditions in each graph are asillustrated below.

(Temperature Condition)

FIG. 13( a), 13(b), 13(c): 4° C.

FIG. 14( a), 14(b), 14(c): 13° C.

FIG. 15( a), 15(b), 15(c): 21° C.

FIG. 16( a), 16(b), 16(c): 30° C.

FIG. 17( a), 17(b), 17(c): 38° C.

(Applied Voltage Condition)

FIG. 13( a), FIG. 14( a), FIG. 15( a), FIG. 16( a), FIG. 17( a): 2100 mV

FIG. 13( b), FIG. 14( b), FIG. 15( b), FIG. 16( b), FIG. 17( b): 2150 mV

FIG. 13( c), FIG. 14( c), FIG. 15( c), FIG. 16( c), FIG. 17( c): 2200 mV

Under the low temperature conditions of 4° C. and 13° C. in which theresponse current is small, a response current that is not dependent inthe Hct value is exhibited in the same manner under any of the appliedvoltage conditions.

Under the high temperature conditions of 30° C. and 38° C. that have alarge response current, a trend is observed for the response current tovary in response to the Hct value. In particular, a conspicuousdifference is observed in the region of 4 seconds or less under anapplied voltage condition of 2.1V and the region of 3 seconds or moreunder an applied voltage condition of 2.2V when compared with an appliedvoltage of 2.15V.

Consequently, it is important to determine an optimal applicationvoltage conditions with reference to the response current in thehigh-temperature region so that the response current is not dependentupon the Hct value under different temperature conditions. The optimalapplication voltage determined in the above manner in Working Example 7is 2.15V. The current value after three seconds is 1.93 μA when theblood sample is introduced at a Hct value of 45% and a temperature of21° C. as shown in Table 2.

TABLE 2 Electrode Surface Area (mm²) Working Counter Optimal AppliedCurrent Value Electrode electrode Voltage (V) (μA) Working 0.12 0.482.15 1.93 Example 7 Working 0.20 0.40 2.1 1.69 Example 8 Working 0.300.30 2.05 1.48 Example 9

Working Example 8

An electrode was formed so that the surface area of the portion 31 ofthe electrode 11 of the sensor chip is 0.20 mm², and the surface area ofthe portion 32 of the electrode 12 of the sensor chip is 0.40 mm². Otherconditions are the same as the sensor chip described in WorkingExample 1. As described in Working Example 7, the optimal appliedvoltage in Working Example 8 determined with reference to the responsecurrent in the high-temperature region is 2.1V. At this time, asillustrated in Table 2, the current value after three seconds is 1.69 μAwhen a blood sample with a Hct value of 45% and a temperature of 21° C.is introduced.

Working Example 9

An electrode was formed so that the surface area of the portion 31 ofthe electrode 11 of the sensor chip is 0.30 mm², and the surface area ofthe portion 32 of the electrode 12 of the sensor chip is 0.30 mm². Otherconditions are the same as the sensor chip described in Working Example1.

As described in Working Example 7, the optimal applied voltage isdetermined with reference to the response current in thehigh-temperature region. The optimal applied voltage in Working Example9 is 2.05V. At this time, as illustrated in Table 2, the current valueafter three seconds is 1.48 μA when a blood sample with a Hct value of45% and a temperature of 21° C. is introduced. The results of WorkingExamples 7, 8 and 9 demonstrate that the dimension of the responsecurrent varied and the optimal applied current is different when theelectrode surface area is different. Furthermore, under a condition inwhich the sum of the surface area of the working electrode is the sameas that of the surface area of the counter electrode, a larger responsecurrent is obtained when the surface area of the counter electrode islarge.

Working Example 10

A sensor chip is prepared as illustrated in FIG. 2 and FIG. 3. Thecapillary is designed with a width of 1.2 mm, a length (depth) of 4.0mm, and a height of 0.15 mm. The insulating plate is formed frompolyethylene terephthalate, and palladium is deposited by vapordeposition onto the insulating plate. Thereafter, the respectiveelectrodes are formed by formation of a slit in the palladium layer witha laser so that the surface area of the portion 31 of the electrode 11is 0.30 mm², and the portion 32 of the electrode 12 is 0.48 mm².

The reaction reagent layer is formed as follows. An aqueous solutionincluding glucose dehydrogenase, potassium ferricyanide (Kanto KagakuCo., Ltd.), taurine (Nakalai Tesque), glucose dehydrogenase wasprepared. The concentration of glucose dehydrogenase is adjusted to aconcentration of 2.0 U/sensor. A concentration of 1.7 mass % ofpotassium ferricyanide, and 1.0 mass % of taurine was dissolved in theaqueous solution to thereby obtain a reagent liquid. After coating ofthe reagent liquid onto the polyethylene terephthalate plate, drying isperformed at a humidity of 45% and a temperature of 21° C.

The Hct value of the blood sample is 25%, 45% and 65%, and the glucoseconcentration is 40 mg/dl, 80 mg/dl, 200 mg/dl, 400 mg/dl, and 1,600mg/dl. The temperature of the blood sample was 4° C., 13° C., 22° C.,30° C., and 39° C.

The application voltage between the electrodes and the application timeis set as follows. 2.075V was applied to both electrodes (temperatureelectrodes) being the electrode 11 (positive electrode) and electrode 12(negative electrode) for 3 seconds from immediately after introductionof the blood sample. From 3 seconds to five seconds, 0.25V was appliedto both electrodes (analysis electrode) being the electrode 13 (positiveelectrode) and electrode 14 (negative electrode), and at five secondsfrom introduction of the blood sample, the measurement is completed.

Table 3 and the graph illustrated in FIG. 18 illustrate the responsecurrent value after three seconds between the temperature electrodes.The response current value after 3 seconds does not depend on the Hctvalue but rather depends on the temperature. The response current valueafter three seconds is converted to the temperature of the blood sampleusing the table illustrated in FIG. 18. A difference is not observed inthe response current value after three seconds at different glucoseconcentrations. Table 4 below illustrates the response current valueafter 5 seconds between the analysis electrodes. The response currentvalue after 5 seconds increases together with increases in the glucoseconcentration at each temperature, or increases together with increasesin the temperature at each glucose concentration. When the temperatureis known, the table illustrated in Table 4 below may be used as aconversion table for glucose concentration to thereby enable conversionof the response current value after 5 seconds to a glucose concentrationfor the blood sample.

TABLE 3 Current value after 3 seconds Hematocrit (μA) 25% 45% 65% Blood 4° C. 0.83 0.82 0.83 Temperature 13° C. 1.16 1.19 1.22 22° C. 1.66 1.631.64 30° C. 2.13 2.12 2.16 39° C. 2.76 2.81 2.80

TABLE 4 Current value after 5 seconds Glucose Concentration (mg/dl) (μA)40 80 200 400 600 Blood  4° C. 1.46 2.35 4.52 6.85 8.31 Temperature 13°C. 1.75 2.85 5.60 9.22 11.89 22° C. 2.15 3.56 6.89 12.03 15.81 30° C.2.48 4.35 8.44 14.82 20.20 39° C. 2.93 4.96 10.50 17.81 23.85

Working Example 11

Four types of sensor chips having the configuration illustrated in FIG.9 and FIG. 10 were prepared. In the first to the four types of sensorchips, the inter-electrode distance illustrated in FIG. 19 isrespectively 100 μm, 300 μm, 500 μm, and 700 μm.

Nine types of blood samples being combinations of three Hct valuesrespectively of 25%, 45% and 65% and three temperatures of 11° C., 21°C., and 30° C. were prepared.

Next, after introduction of the blood samples above into the capillaryin the sensor chips above, a 2.2V voltage was applied between theelectrodes (temperature electrodes), and the respective responsecurrents were measured.

The measurement results are illustrated in the graphs in FIGS. 20(a)-20(d), FIGS. 21( a)-21(d), and FIGS. 22( a)-22(d). FIGS. 20( a)-20(d)illustrate the response current value in an 11° C. blood sample byinter-electrode distance and by hematocrit. FIGS. 21( a)-21(d)illustrate the response current value in a 21° C. blood sample byinter-electrode distance and by hematocrit. FIGS. 22( a)-22(d)illustrate the response current value in a 30° C. blood sample byinter-electrode distance and by hematocrit.

The graphs above do not exhibit a significant difference in the responsecurrent value when the inter-electrode distance is varied. The resultsof Working Example 11 demonstrate that the response current exhibitsalmost no effect due to the inter-electrode distance.

Working Example 12

Two types of sensor chips having different electrode shapes wereprepared.

A first type of sensor chip has the configuration illustrated in FIG. 9,FIG. 10 and FIG. 23( a). In the first type of sensor chip, the surfacearea of the portion 31 (working electrode) of the electrode 11 is 0.24mm², and the surface area of the portion 32 (counter electrode) of theelectrode 12 of the sensor chip is 0.96 mm², and the inter-electrodedistance is 300 μm.

A second type of sensor chip has the configuration illustrated in FIG.23( b). In the second type of sensor chip, the surface area of theportion 31 (working electrode) of the electrode 11 is 0.24 mm², and theportion 32 (counter electrode) of the electrode 12 has a shape that isformed separately at two positions in FIG. 23( b). The surface area ofthe two portions of the portion 32 are respectively 0.48 mm². The totalvalue for the portion 32 of the electrode 12 is 0.96 mm². In the secondtype of sensor chip, the inter-electrode distance is 300 μm.

Nine types of blood samples being combinations of three Hct valuesrespectively of 25%, 45% and 65% and three temperatures of 11° C., 21°C., and 30° C. were prepared.

Next, after introduction of the blood samples above into the capillaryin the sensor chips above, a 2.2V voltage was applied between theelectrodes (temperature electrodes), and the respective responsecurrents were measured.

The measurement results are illustrated in the graphs in FIGS. 24(a)-24(b), FIGS. 25( a)-25(b), and FIGS. 26( a)-26(b). FIGS. 24( a)-24(b)illustrate the response current value in an 11° C. blood sample byelectrode shape and by hematocrit. FIGS. 25( a)-25(b) illustrate theresponse current value in a 21° C. blood sample by electrode shape andby hematocrit. FIGS. 26( a)-26(b) illustrate the response current valuein a 30° C. blood sample by electrode shape and by hematocrit.

The graphs above do not exhibit a significant difference in the responsecurrent value when the electrode shape distance is varied. The resultsof Working Example 12 demonstrate that the response current exhibitsalmost no effect due to the electrode shape.

Working Example 13

Four types of sensor chips having different lead widths in the counterelectrode 12 were prepared. The respective types of sensor chip have theconfiguration illustrated in FIG. 2, FIG. 3 and FIG. 27( a). In eachtype of sensor chip, the surface area of the portion 31 (workingelectrode) of the electrode 11 is 0.30 mm², and the portion 32 (counterelectrode) of the electrode 12 is 0.30 mm², and the inter-electrodedistance is 100 μm. In the first to the fourth types of sensor chip, thelead width in the counter electrode 12 illustrated in FIG. 27( b) isrespectively 0.5 mm, 1.0 mm, 1.5 mm, 2.0 mm.

Three types of blood samples were prepared. The Hct values for a firstto a third type of blood sample are respectively 25%, 45% and 65% and atemperature for each type of blood sample is 23° C. (room temperature).

Next, after introduction of the blood samples above into the capillaryin the sensor chips above, a 2.05V voltage was applied between theelectrodes (temperature electrodes), and the respective responsecurrents were measured.

The measurement results are illustrated in the graphs in FIGS. 28(a)-28(d). These graphs demonstrate that the response current exhibitsalmost no change even at different hematocrit values. Furthermore, asignificant difference is not observed in the response current valuewhen the lead width is varied. The results of Working Example 13demonstrate that the response current exhibits almost no effect due tothe lead width (resistance).

Working Example 14

Two types of sensor chips were prepared. A first and a second type ofsensor chip have the configuration illustrated in FIG. 9 and FIG. 10. Inthe first and the second type of sensor chip, the surface area of theportion 31 (working electrode) of the electrode 11 is 0.12 mm², and thesurface area of the portion 32 (counter electrode) of the electrode 12of the sensor chip is 0.48 mm², and the inter-electrode distance is 300μm. In the first type and the second type of sensor chip, the thicknessof the spacer 202 illustrated in FIG. 29 (capillary height) isrespectively 0.15 mm and 0.09 mm.

Nine types of blood samples being combinations of three Hct valuesrespectively of 25%, 45% and 65% and three temperatures of 11° C., 21°C., and 30° C. were prepared.

Next, after introduction of the blood samples above into the capillaryin the sensor chips above, a 2.2V voltage was applied between theelectrodes (temperature electrodes), and the respective responsecurrents were measured.

The measurement results are illustrated in the graphs in FIGS. 30(a)-30(b), FIGS. 31( a)-31(b), and FIGS. 32( a)-32(b). FIGS. 30( a)-30(b)illustrate the response current value in an 11° C. blood sample bycapillary height and by hematocrit. FIGS. 31( a)-31(b) illustrate theresponse current value in a 21° C. blood sample by capillary height andby hematocrit. FIGS. 32( a)-32(b) illustrate the response current valuein a 30° C. blood sample by capillary height and by hematocrit.

The graphs above do not exhibit a significant difference in the responsecurrent value even when the capillary height is varied. The results ofWorking Example 14 demonstrate that the response current exhibits almostno effect due to the capillary height.

Working Example 15

Two types of sensor chips were prepared. The respective types of sensorchip have the configuration illustrated in FIG. 9 and FIG. 10. In eachtype of sensor chip, the surface area of the portion 31 (workingelectrode) of the electrode 11 is 0.12 mm², and the surface area of theportion 32 (counter electrode) of the electrode 12 of the sensor chip is0.48 mm², and the inter-electrode distance is 100 μm. The surfaceresistance of the palladium vapor-deposited plate of the first type andthe second type of sensor chip is respectively 115 Ω/□ and 60 Ω/□.

Fifteen types of blood samples being combinations of three Hct valuesrespectively of 25%, 45% and 65% and the temperatures of 4° C., 13° C.,21° C., 30C., and 38° C. were prepared.

Next, after introduction of the above blood samples above into the abovecapillary in the sensor chips, a 2.15V voltage was applied between theelectrodes (temperature electrodes), and the respective responsecurrents were measured.

The measurement results are illustrated in the graphs in figures (a) and(b) in FIGS. 33-37. FIGS. 33( a) and 33(b) illustrate the responsecurrent value in a 4° C. blood sample by palladium resistance. FIGS. 34(a) and 34(b) illustrate the response current value in a 13° C. bloodsample by palladium resistance. FIGS. 35( a) and 35(b) illustrate theresponse current value in a 21° C. blood sample by palladium resistance.FIGS. 36( a) and 36(b) illustrate the response current value in a 30° C.blood sample by palladium resistance. FIGS. 37( a) and 37(b) illustratethe response current value in a 38° C. blood sample by palladiumresistance.

The graphs above do not exhibit a significant difference in the responsecurrent value when palladium resistance is varied. The results ofWorking Example 15 demonstrate that the response current exhibits almostno effect due to the palladium resistance. There is no necessity toexplain that when a known conductive material such as platinum, gold,silver, titanium, copper, nickel, and carbon is applied to the plate,the same effect is obtained.

Working Example 16

Sensor chips were prepared to have the configuration illustrated in FIG.9 and FIG. 10. In the sensor chips, the surface area of the portion 31(working electrode) of the electrode 11 is 0.12 mm², the surface area ofthe portion 32 (counter electrode) of the electrode 12 of the sensorchip is 0.48 mm², and the inter-electrode distance is 100 μm.

Three types of blood samples were prepared by adding a glucoseconcentrate to blood having a Hct value of 45% and a temperature of 24°C. The glucose concentrations of the first to the third blood sample arerespectively 0 mg/dL, 205 mg/dL, and 640 mg/dL.

Next, the above blood samples were introduced into the capillaries ofthe respective sensor chips above. Thereafter, a voltage of 2.15V wasapplied between the electrodes (temperature electrodes), and therespective response currents were measured.

The measurement results are illustrated in the graph in FIG. 38. FIG. 38illustrates the response current value in a 24° C. blood sample byglucose concentration. The graphs above do not exhibit a significantdifference in the response current value when glucose concentration isvaried. The results of Working Example 16 demonstrate that the responsecurrent exhibits almost no effect due to glucose concentration. When thepresent invention is applied to a blood glucose sensor (glucose sensor),since the measurements are not affected by the glucose concentration, itis shown that application is possible without problems.

Working Example 17

Sensor chips were prepared as in FIG. 9 and FIG. 10 so that the surfacearea of the portion 31 (working electrode) of the electrode 11 is 0.12mm², the surface area of the portion 32 (counter electrode) of theelectrode 12 of the sensor chip is 0.48 mm², and the inter-electrodedistance is 100 μm.

Three types of blood samples with different ascorbic acid concentrationswere prepared by adding an ascorbic acid concentrate to blood having aHct value of 45% and a temperature of 24° C. The glucose concentrationsof the first to the third blood sample are respectively 0 mg/dL, 10mg/dL, and 20 mg/dL.

Next, the above blood samples were introduced into the capillaries ofthe respective sensor chips above. Thereafter, a voltage of 2.15V wasapplied between the electrodes (temperature electrodes), and therespective response currents were measured.

The measurement results are illustrated in the graph in FIG. 39. FIG. 39illustrates the response current value in a 24° C. blood sample byascorbic acid concentration. The graphs above do not exhibit asignificant difference in the response current value when ascorbic acidconcentration is varied. That is to say, in the present working example,the measurement accuracy for blood glucose level was not affected by theserum concentration of ascorbic acid, that is a reducing substance.Therefore it is shown that the sensor chip according to the presentworking example can be used without problems as a blood glucose levelsensor.

Working Example 18

Sensor chips were prepared to have the configuration illustrated in FIG.9 and FIG. 10. In the sensor chips, the surface area of the portion 31(working electrode) of the electrode 11 is 0.12 mm², the surface area ofthe portion 32 (counter electrode) of the electrode 12 of the sensorchip is 0.48 mm², and the inter-electrode distance is 100 μm.

Two types of blood samples having different temperatures were prepared.A first type of blood sample has a Hct value of 45% and a temperature of4° C. A second type of blood sample has a Hct value of 45% and atemperature of 42° C.

Next, one minute after moving the above blood samples to a 24° C.environment, the samples were introduced into the capillaries of therespective sensor chips described above. Thereafter, a voltage of 2.15Vwas applied between the electrodes (temperature electrodes), and therespective response currents were measured.

The measurement results are illustrated in the graph in FIG. 40. Thedotted line in FIG. 40 illustrates the response current value whenintroducing blood at 24° C. to a 24° C. environment (hereinafterreferred to as “normal introduction”). The solid line in FIG. 40illustrates the response current value when introducing blood at 4° C.to a 24° C. environment (hereinafter referred to as “4° C.introduction”). The broken line in FIG. 40 illustrates the responsecurrent value when introducing blood at 42° C. to a 24° C. environment(hereinafter referred to as “42° C. introduction”).

The graphs illustrate that during a time period soon after themeasurement period, the temperature exhibited by the 4° C. introductionis low in comparison to the temperature exhibited by the normalintroduction, and the temperature exhibited by the 42° C. introductionis high in comparison to the temperature exhibited by the normalintroduction. Over the passage of time during the measurement period,the temperature difference between the 42° C. introduction and the 4° C.introduction disappears. The fact that the temperature differencedisappears due to the passage of the measurement period is thought inboth cases to result from the movement of the blood sample at 4° C. or42° C. to a 24° C. environment, and therefore over the passage of time,both samples shift to 24° C. that is the temperature of the sensor chip.

According to Working Example 18, it is shown that measurement oftemporal variation in relation to the temperature of the blood sample ispossible.

Furthermore, the sensor chip is provided with a temperature electrodethat is disposed to make contact with the blood sample, and measures thetemperature of the blood sample. Therefore, when the sensor chip isused, a temperature for the blood sample that takes into considerationtemporal variation can be obtained, and this value can be used tocorrect the glucose concentration and the like. In other words, theaccuracy of various types of corrections can be improved.

Working Example 19

Sensor chips were prepared to have the configuration illustrated in FIG.9 and FIG. 10. In the sensor chips, the surface area of the portion 31(working electrode) of the electrode 11 is 0.12 mm², the surface area ofthe portion 32 (counter electrode) of the electrode 12 of the sensorchip is 0.48 mm², and the inter-electrode distance is 100 μm.

A blood sample was prepared. The blood sample has a Hct value of 45%.

As illustrated in FIG. 41, approximately 3 μL of blood was dripped inadvance into the sensor chip. The blood was dripped onto an upperportion of the cover 203. Dripping blood in this manner is hereinafterreferred to as “upward orientation”.

Approximately 10 μL of blood was dripped in advance into the othersensor chip. The blood was dripped onto a lower portion of theinsulating plate 201. Dripping blood in this manner is hereinafterreferred to as “downward orientation”.

Next, the above blood samples were introduced in a 24° C. environmentinto the capillaries 204 of the respective sensor chips. Thereafter, avoltage of 2.15V was applied between the electrodes (temperatureelectrodes), and the respective response currents were measured.

The measurement results are illustrated in the graph in FIG. 42. Thebroken line in FIG. 42 illustrates the response current when drippingblood in advance in an upward orientation in a 24° C. environment. Thesolid line in FIG. 42 illustrates the response current when drippingblood in advance in a downward orientation in a 24° C. environment. Thedotted line in FIG. 42 illustrates the response current when drippingblood in advance in both an upward orientation and a downwardorientation in a 24° C. environment (hereinafter referred to as “normalintroduction”).

The graphs illustrate that in comparison to normal introduction, theresponse current value is low during an upward orientation and during adownward orientation. This is thought to be due to the fact that thetemperature of the blood sample in the capillary 204 is reduced by theheat of evaporation of blood in an upward orientation and during adownward orientation that becomes excessively attached to an outer rangeof the capillary 204.

Working Example 19 enables comprehension of the effect of heat ofevaporation as illustrated in FIG. 42.

The sensor chip is provided with a temperature electrode that isdisposed to make contact with the blood sample, and that measures thetemperature of the blood sample. Therefore, a temperature for the bloodsample that takes into consideration heat of evaporation can beobtained, and this value can be used to correct the glucoseconcentration and the like. In other words, the accuracy of varioustypes of corrections can be improved.

Working Example 20

Sensor chips were prepared to have the configuration illustrated in FIG.9 and FIG. 10 in that the surface area of the portion 31 (workingelectrode) of the electrode 11 is 0.12 mm², the surface area of theportion 32 (counter electrode) of the electrode 12 of the sensor chip is0.48 mm², and the inter-electrode distance is 100 μm. A blood samplewith a Hct value of 45% was prepared.

Immediately after the distal end of the sensor chip gripped in thefingers for 5 seconds is mounted onto the measuring device, andimmediately after the distal end of the sensor chip not gripped in thefingers is mounted onto the measuring device, the blood sample above isintroduced in a 24° C. environment. Thereafter, a voltage of 2.15V wasapplied between the electrodes (temperature electrodes), and therespective response currents were measured.

The measurement results are illustrated in the graph in FIG. 43. Thesolid line in FIG. 43 illustrates the response current when the distalend of the sensor chip is gripped in the fingers for 5 seconds in a 24°C. environment. The solid line in FIG. 43 illustrates the responsecurrent when the distal end of the sensor chip is not gripped in thefingers for 5 seconds in a 24° C. environment (hereinafter referred toas normal introduction”).

According to Working Example 20, an error in the finger tip temperatureas illustrated in FIG. 43 can be comprehended.

The sensor chip according to the present invention is provided with atemperature electrode that is disposed to make contact with the bloodsample, and that measures the temperature of the blood sample.Therefore, a temperature for the blood sample that takes intoconsideration finger-tip temperature can be obtained, and this value canbe used to correct the glucose concentration and the like. In otherwords, the accuracy of various types of corrections can be improved.

Working Example 21

Sensor chips as described in Working Example 10 were prepared asillustrated in FIG. 2 and FIG. 3 in that the surface area of the portion31 (working electrode) of the electrode 11 is 0.30 mm², the surface areaof the portion 32 (counter electrode) of the electrode 12 of the sensorchip is 0.48 mm², and the inter-electrode distance is 100 μm. Bloodsamples with a glucose concentration of 209 mg/dL, Hct values of 25%,45%, and 65% were prepared at a temperature of 22° C.

Next, after introduction of the blood samples into the capillary of thesensor chips as described above, a predetermined voltage was appliedbetween predetermined electrodes in the order illustrated in FIG. 44. Inother words, from 0 seconds to 3.0 seconds, a voltage of 2075 mV isapplied to electrode 11 and electrode 12 (electrodes 11-12 in FIG. 44).Then from 3.0 seconds to 5.0 seconds, a voltage of 250 mV is applied toelectrode 13 and electrode 14 (electrodes 13-14 in FIG. 44). Then from5.1 seconds to 5.5 seconds, a voltage of 2500 mV is applied to electrode11 and electrode 13 (electrodes 11-13 in FIG. 44). The respectiveresponse currents were measured.

The measurement results are illustrated by the graph in FIG. 45( a) andFIG. 45( b). These graphs illustrate that a response current valueaccording to the hematocrit value can be obtained when using glucose orHct (hematocrit) as a measurement target. Furthermore as illustrated inFIG. 46( a), a response current value can be obtained in relation to apredetermined temperature as illustrated in FIG. 46( b) in relation totemperature.

According to Working Example 21, it is shown that measurement insequence is possible in relation to respective features such as glucose,temperature or Hct.

The measurement sequence of glucose, temperature and Hct is not fixed tothe sequence above, and may be executed in an arbitrary sequence. Forexample, the sequence of temperature, Hct and glucose is possible.

As illustrated in FIG. 47, measurement is possible in relation tofeatures including glucose, temperature, Hct and a reducing substance.In other words, as illustrated in FIG. 47, a voltage may be applied from0 seconds to 3.0 seconds to electrode 11 and electrode 12 (electrodes11-12 in FIG. 47), from 3.0 seconds to 4.95 seconds to electrode 12 andelectrode 14 (electrodes 12-14 in FIG. 47), then substantially at thesame time, from (3 seconds to 5.0 seconds), to electrode 13 andelectrode 14 (electrodes 13-14 in FIG. 47), and from 5.1 seconds to 5.5seconds to electrode 11 and electrode 13 (electrodes 11-13 in FIG. 47).This configuration also obtains a response current that corresponds tothe respective conditions.

When measuring two or more features at the same time, care is requiredto avoid mixing combinations of the working electrode and the counterelectrode. For example, when measuring glucose at the same time astemperature, it is preferred to measure the response current of theglucose measurement with electrode 13 and electrode 14 (electrodes 13-14in FIG. 47), and the response current of the temperature measurementwith electrode 11 and electrode 12 (electrodes 11-12 in FIG. 47). Whenthe glucose response current flows between electrodes 13-12 or thetemperature response current flows between electrodes 11-14, the desiredresponse current cannot be obtained. As a result, when measuring two ormore features at the same time, it is important to select suitablecombinations of electrodes for application of voltage, suitableapplication voltage and application time in order to avoid the mixing asdescribed above.

Modified Example 1

As illustrated in FIG. 6( a), in another embodiment, the step ofdetermining the analyte concentration in the blood sample in step S4(concentration determination step) was explained with reference to anexample including step S101 to step S106. However the invention is notlimited in this regard.

For example, as illustrated in FIG. 48( a), the concentrationdetermination step S4 may include a step 141 for correcting the data bbased on the data a. The computing unit (concentration determinationunit) 306 in the biosensor system 100 (refer to FIG. 4) includes a firstanalyte correcting unit 321 configured to correct the data b based onthe data a as illustrated in FIG. 50( a).

Furthermore, as illustrated in FIG. 48( b), the concentrationdetermination step S4 may include a step S241 for calculating of theconcentration x of the analyte in the blood sample based on the data band a step S242 for correcting the concentration x based on the data a.The computing unit (concentration determination unit) 306 in thebiosensor system 100 (refer to FIG. 4) includes a concentrationcalculating unit 331 configured to calculate a concentration x of ananalyte in the blood sample based on data b, and a second analytecorrecting unit 332 configured to correct a concentration x based on thedata a as illustrated in FIG. 50( b).

As illustrated in FIG. 49( a), the concentration determination step S4may include a step S341 for calculating the temperature t of the bloodsample based on the data a, and a step S342 for correcting the data bbased on the temperature t. The computing unit (concentrationdetermination unit) 306 in the biosensor system 100 (refer to FIG. 4)includes a temperature calculating unit 341 configured to calculate atemperature t of the blood sample based on data a, and a third analytecorrecting unit 342 configured to correct the data b based on thetemperature t as illustrated in FIG. 51( a).

As illustrated in FIG. 49( b), the concentration determination step S4may include a step S441 for calculating the temperature t of the bloodsample based on the data a, and a step S442 for calculating theconcentration x of the analyte in the blood sample based on the data b.The computing unit (concentration determination unit) 306 in thebiosensor system 100 (refer to FIG. 4) includes a temperaturecalculating unit 351 configured to calculate a temperature t of theblood sample based on data a, a concentration calculating unit 352configured to calculate a concentration x of the analyte in the bloodsample based on the data b, and a fourth analyte correcting unit 353configured to correct the concentration x based on the temperature t asillustrated in FIG. 51( b).

Modified Example 2

The control circuit 300 in the above embodiment as illustrated in FIG.52 may be further provided with a sequence control unit 501 and anelectrode selection unit 502.

The sequence control unit 501 may control the control circuit 300 tosimultaneously measure at least two features when measuring temperature,glucose, hematocrit, or a reducing substance. Furthermore the sequencecontrol unit 501 may control the control circuit 300 to performindependent measurements when measuring temperature, glucose,hematocrit, or a reducing substance. The sequence of measuring theserespective features is arbitrary. The sequence control unit 501 maycontrol the control circuit 300 to perform independent measurements inthe sequence of temperature, glucose and a reducing substance, andhematocrit when measuring temperature, glucose, hematocrit, or areducing substance.

The electrode selection unit 502 may control the control circuit 300 toperform measurements through independent electrodes when measuringtemperature, glucose, hematocrit, or a reducing substance.

INDUSTRIAL APPLICABILITY

During measurement of an analyte in a blood sample, the presentinvention suppresses the production of a measurement error caused bytemperature when executing measurements, and therefore has useful valuein broad technical areas that require high measurement accuracy.

REFERENCE NUMBERS

-   11, 12, 13, 14, 15 ELECTRODE (VOLTAGE APPLICATION PORTION)-   16 DISCHARGE PORT-   17 BLOOD SAMPLE INTRODUCTION PORT-   20 REACTION REAGENT LAYER-   31 PORTION OF ELECTRODE 11 FACING CAPILLARY-   32 PORTION OF ELECTRODE 12 FACING CAPILLARY-   33 PORTION OF ELECTRODE 13 FACING CAPILLARY-   34 PORTION OF ELECTRODE 14 FACING CAPILLARY-   35 PORTION OF ELECTRODE 15 FACING CAPILLARY-   40 CAPILLARY-   41 MEASURING UNIT A (TEMPERATURE MEASURING UNIT)-   42 MEASURING UNIT B (ANALYTE MEASURING UNIT)-   100 BIOSENSOR SYSTEM-   101 MEASURING DEVICE-   102 MOUNTING PORT-   103 DISPLAY UNIT-   200 SENSOR CHIP-   201 INSULATING PLATE-   202 SPACER-   203 COVER-   204 NOTCH-   210 SENSOR CHIP-   300 CONTROL CIRCUIT-   301 a, 301 b, 301 c, 301 d, 301 e CONNECTOR-   302 SWITCHING CIRCUIT-   303 CURRENT/VOLTAGE CONVERSION CIRCUIT-   304 ANALOG/DIGITAL (A/D) CONVERSION CIRCUIT-   305 REFERENCE VOLTAGE POWER SOURCE-   306 COMPUTING UNIT (CONCENTRATION DETERMINATION UNIT)-   307 TEMPERATURE MEASURING UNIT-   308 COMPUTING UNIT-   309 CONCENTRATION CALCULATING UNIT-   310 TEMPERATURE CALCULATING UNIT-   311 CONCENTRATION CALCULATING UNIT-   312 ENVIRONMENTAL TEMPERATURE MEASURING-   UNIT-   313 COMPARISON UNIT-   314 CORRECTION UNIT-   315 ENVIRONMENTAL TEMPERATURE MEASURING-   UNIT-   321 FIRST ANALYTE CORRECTION UNIT-   331 CONCENTRATION CALCULATING UNIT-   332 SECOND ANALYTE CORRECTION UNIT-   341 TEMPERATURE CALCULATING UNIT-   342 THIRD ANALYTE CORRECTION UNIT-   351 TEMPERATURE CALCULATING UNIT-   352 CONCENTRATION CALCULATING UNIT-   353 FOURTH ANALYTE CORRECTION UNIT-   400 DISPLAY UNIT-   501 SEQUENCE CONTROL UNIT-   502 ELECTRODE SELECTION UNIT-   S STEP

1. A sensor chip for measuring the temperature of a biological sample,the sensor chip comprising: temperature electrodes having at least aworking electrode and an counter electrode, the electrodes for measuringthe temperature of the biological sample and having a direct currentvoltage applied thereto; and a capillary configured to introduce thebiological sample to the temperature electrodes; wherein the workingelectrode and/or the counter electrode in the temperature electrodes aredisposed to make contact with the biological sample introduced into thecapillary, and the direct current voltage is set to reduce an effect ofhematocrit on a temperature measurement result during application of thedirect current voltage.
 2. The sensor chip according to claim 1 whereinthe uptake amount of the biological sample into the capillary is 5 μL orless, and the application time of the direct current voltage to thetemperature electrodes is 15 seconds or less.
 3. The sensor chipaccording to claim 1 wherein the predetermined direct current voltage iswithin a range in which the solvent of the biological sample issubjected to electrolysis.
 4. The sensor chip according to claim 1wherein the sensor chip is disposable.
 5. A sensor chip for measuringthe concentration of an analyte in a blood sample, the sensor chipcomprising: temperature electrodes disposed to make contact with theblood sample, the temperature electrodes having at least a workingelectrode and a counter electrode for measuring the temperature of theblood sample; and a concentration measuring unit configured to measure afeature related to a concentration of the analyte in the blood sample.6. The sensor chip according to claim 5 wherein the concentrationmeasuring unit is formed from analysis electrodes including at least aworking electrode and a counter electrode.
 7. The sensor chip accordingto claim 6 wherein the temperature electrodes and the analysiselectrodes are provided separately.
 8. The sensor chip according toclaim 6 wherein further comprising: a sample introduction port; and acapillary configured to introduce a blood sample from the sampleintroduction port to the temperature electrodes and the analysiselectrodes; and wherein the temperature electrodes are disposed at aposition closer to the sample introduction port than the analysiselectrodes.
 9. The sensor chip according to claim 5 wherein theconcentration measuring unit further includes an oxidoreductase and anelectron mediator, and the temperature electrodes are disposed to notmake contact with at least one of the oxidoreductase or the electronmediator.
 10. The sensor chip according to claim 5 wherein theconcentration measuring unit further includes a reaction reagent thatinduces an oxidation-reduction reaction, and the temperature electrodesare disposed to not make contact with the reaction reagent that inducesthe oxidation-reduction reaction.
 11. The sensor chip according to claim5 wherein the concentration measuring unit further includes a reagent,and the temperature electrodes are disposed to not make contact with anyreagent.
 12. The sensor chip according to claim 6 wherein the workingelectrode of the temperature electrodes is common to at least either theworking electrode or the counter electrode of the analysis electrodes.13. The sensor chip according to claim 6 wherein the counter electrodeof the temperature electrodes is common to at least either the workingelectrode or the counter electrode of the analysis electrodes.
 14. Thesensor chip according to claim 6 wherein the concentration measuringunit includes at least one electrode in addition to the workingelectrode and the counter electrode, and the at least one electrode ofthe concentration measuring unit other than the working electrode andthe counter electrode is common to at least one of the working electrodeand the counter electrode of the temperature electrodes.
 15. The sensorchip according to claim 6 wherein the surface area of the workingelectrode in the temperature electrodes is either the same or smallerthan the surface area of the counter electrode in the temperatureelectrodes.
 16. The sensor chip according to claim 5 wherein at leasthematocrit is included as a feature in relation to the concentration ofthe analyte.
 17. The sensor chip according to claim 5 wherein at least aconcentration or an amount of a reducing substance is included as afeature in relation to the concentration of the analyte.
 18. A methodfor measuring a temperature of a biological sample with a sensor chip,the sensor chip including temperature electrodes formed from a workingelectrode and a counter electrode, and a capillary, the methodcomprising the steps of: introducing a biological sample by thecapillary to the temperature electrodes; applying a direct currentvoltage to the temperature electrodes; and adjusting the direct currentvoltage applied in the application step to a first voltage, and wherein:the first voltage is set to reduce an effect of hematocrit on atemperature measurement result during application of the first voltageto the temperature electrodes.
 19. The method for measuring atemperature of a biological sample according to claim 18 comprising thefurther step of: measuring and storing in advance a direct currentvoltage that enables a reduction of the effect of hematocrit on thetemperature measurement result; and the adjustment step adjusts to thefirst voltage based on the stored direct current voltage.
 20. The methodfor measuring a temperature of a biological sample according to claim18, wherein the uptake amount of the biological sample in the uptakestep is 5 μL or less, and the application time of the direct currentvoltage in the application step is 15 seconds or less.
 21. A method formeasuring a temperature of a blood sample using a sensor chip, thesensor chip including temperature electrodes formed from a workingelectrode and a counter electrode, the method comprising the steps of:applying a voltage to the temperature electrodes in contact with theblood sample; acquiring data a related to the temperature of the bloodsample based on a dimension of a current flowing in the blood sample byapplication of the voltage; and calculating a temperature t of the bloodsample based on the data a.
 22. A method for measuring a concentrationof an analyte in a blood sample comprising the steps of: acquiring dataa related to the temperature of the blood sample based on the dimensionof a current flowing in the blood sample by application of a voltage tothe pair of electrodes in contact with the blood sample; acquiring datab related to a concentration of the analyte based on the dimension of acurrent flowing in the blood sample by a reaction mediated by anoxidoreductase that uses the analyte in the blood sample as a substrate;and measuring a concentration that determines the analyte concentrationin the blood sample based on the data a and the data b.
 23. The methodfor measuring a concentration of an analyte in a blood sample accordingto claim 22, wherein the concentration measurement step includes a stepof correcting the data b based on the data a.
 24. The method formeasuring a concentration of an analyte in a blood sample according toclaim 22, wherein the concentration measurement step includes a step ofcalculating a concentration x of an analyte in a blood sample based onthe data b, and a step of correcting the concentration x based on thedata a.
 25. The method for measuring a concentration of an analyte in ablood sample according to claim 22, wherein the concentrationmeasurement step includes a step of calculating a temperature t of theanalyte in the blood sample based on the data a, and a step ofcorrecting the data b based on the temperature t.
 26. The method formeasuring a concentration of an analyte in a blood sample according toclaim 22, wherein the concentration measurement step includes a step ofcalculating a temperature t of an analyte in a blood sample based on thedata a, a step of calculating a concentration x of the analyte in ablood sample based on the data b, and a step of correcting theconcentration x based on the temperature t.
 27. The method for measuringa concentration of an analyte in a blood sample according to claim 22,wherein the step of acquiring the data a is performed in advance of thestep of acquiring the data b.
 28. The method for measuring aconcentration of an analyte in a blood sample according to claim 22,wherein the concentration measurement step includes a step of acquiringdata c related to the temperature of the blood sample based on thedimension of a current flowing in the blood sample by application of apredetermined voltage to the pair of electrodes in contact with theblood sample after acquisition of the data b, a step of calculating datad related to the temperature of the blood sample based on the data a andthe data c, and a step of correcting the data b based on the data d. 29.The method for measuring a concentration of an analyte in a blood sampleaccording to claim 22, wherein the concentration measurement stepincludes a step of calculating the temperature t of the blood samplebased on the data a, a step of calculating the concentration x of theanalyte in the blood sample based on the data b, the step of measuringan environmental temperature t1 in a periphery of the blood sample, astep of comparing the difference between the temperature t and theenvironmental temperature t1 with a temperature threshold Z, and a stepof correcting the concentration x based on the temperature t when therelation |t−t1|≧Z is satisfied, and correcting the concentration x basedon the temperature t1 when the relation |t−t1|<Z is satisfied.
 30. Themethod for measuring a concentration of an analyte in a blood sampleaccording to claim 22, wherein a temperature is contained in the data arelated to the temperature of the blood sample, and a glucoseconcentration is contained in the data b related to the concentration ofthe analyte.
 31. The method for measuring a concentration of an analytein a blood sample according to claim 30, wherein hematocrit is includedin the data b related to the concentration of the analyte.
 32. Themethod for measuring a concentration of an analyte in a blood sampleaccording to claim 30, wherein the concentration or amount of a reducingsubstance is contained in the data b related to the concentration of theanalyte.
 33. The method for measuring a concentration of an analyte in ablood sample according to claim 30, wherein at least two features of thedata included in the data a and the data b are measured at the sametime.
 34. The method for measuring a concentration of an analyte in ablood sample according to claim 30, wherein the respective data includedin the data a and the data b are measured independently.
 35. The methodfor measuring a concentration of an analyte in a blood sample accordingto claim 30, wherein the measurement of the data contained in the data aand the data b is performed in order of temperature, glucoseconcentration, concentration or amount of the reducing substance, andhematocrit.
 36. The method for measuring a concentration of an analytein a blood sample according to claim 30, wherein the measurement of thedata contained in the data a and the data b is performed throughindependent electrodes.
 37. A biosensor system for measuring aconcentration of an analyte in a blood sample, the biosensor systemcomprising the sensor chip according to claim 1 that includes thetemperature electrodes, and a measuring device including a controlcircuit configured to apply a voltage to the temperature electrodes ofthe sensor chip, the biosensor system comprising: a voltage applicationunit configured to apply a voltage to the temperature electrodes inaccordance with the control circuit; a temperature measuring unitconfigured to acquire the data a related to the temperature of the bloodsample based on the dimension of a current flowing in the temperatureelectrodes in contact with the blood sample; an analyte measuring unitacquiring data b related to the concentration of the analyte based onthe dimension of a current flowing in the blood sample depending on areaction mediated by an oxidoreductase that uses the analyte in theblood sample as a substrate; and a concentration determination unitconfigured to determine an analyte concentration in the blood samplebased on the data a and the data b.
 38. The biosensor system accordingto claim 37 wherein the concentration determination unit includes afirst analyte correction unit configured to correct the data b based onthe data a.
 39. The biosensor system according to claim 37 wherein theconcentration determination unit includes a calculating unit configuredto calculate the concentration x of the analyte of the blood samplebased on the data b; and a second analyte correction unit configured tocorrect the concentration x based on the data a.
 40. The biosensorsystem according to claim 37 wherein the concentration determinationunit includes a calculating unit configured to calculate the temperaturet of the blood sample based on the data a; and a third analytecorrection unit configured to correct the data b based on thetemperature t.
 41. The biosensor system according to claim 37 whereinthe concentration determination unit includes a calculating unitconfigured to calculate the temperature t of the blood sample based onthe data a; a calculating unit configured to calculate the concentrationx of the blood sample based on the data b; and a fourth analytecorrection unit configured to correct the concentration x based on thetemperature t.
 42. The biosensor system according to claim 37, whereinthe data b related to the concentration of the analyte is acquired bythe analyte measuring unit after acquisition of the data a related tothe temperature of the sample by the temperature measuring unit.
 43. Thebiosensor system according to claim 37 wherein the concentrationdetermination unit includes a temperature measuring unit configured toacquire data c related to the temperature of the blood sample based onthe dimension of a current flowing in the blood sample by application ofa predetermined voltage to the pair of electrodes in contact with theblood sample after acquisition of the data b; a computing unitconfigured to calculate data d related to the temperature of the bloodsample based on the data a and the data c; and a calculating unitconfigured to calculate the concentration x of the analyte corrected inresponse to the temperature of the blood sample based on the data d. 44.The biosensor system according to claim 37 wherein the concentrationdetermination unit includes a temperature calculating unit configured tocalculate the temperature t of the blood sample based on the data a; aconcentration calculating unit configured to calculate the concentrationx of the analyte in the blood sample based on the data b; anenvironmental temperature measuring unit configured to measure anenvironmental temperature t1 in a periphery of the blood sample; acomparison unit configured to compare the difference between thetemperature t and the environmental temperature t1 with a temperaturethreshold Z; and a correction unit configured to correct theconcentration x based on the temperature t when the relation |t−t1|≧Z issatisfied, and correcting the concentration x based on the temperaturet1 when the relation |t−t1|<Z is satisfied.
 45. The biosensor systemaccording to claim 37, wherein a temperature is contained in the data arelated to the temperature of the blood sample, and a glucoseconcentration is contained in the data b related to the concentration ofthe analyte.
 46. The biosensor system according to claim 45 whereinhematocrit is included in the data b related to the analyteconcentration.
 47. The biosensor system according to claim 45 whereinthe concentration or amount of the reducing substance is contained inthe data b related to the concentration of the analyte.
 48. Thebiosensor system according to claim 45, further comprising a sequencecontrol unit configured to control the control circuit to measure atleast two features of the data included in the data a and the data b atthe same time.
 49. The biosensor system according to claim 45, furthercomprising a sequence control unit configured to control the controlcircuit to execute independent measurement of the respective dataincluded in the data a and the data b.
 50. The biosensor systemaccording to claim 45, further comprising a sequence control unitconfigured to control the control circuit to measure the data containedin the data a and the data b in order of temperature, glucoseconcentration, concentration or amount of the reducing substance, orhematocrit.
 51. The biosensor system according to claim 45, furthercomprising an electrode selection unit configured to control the controlcircuit to measure the data contained in the data a and the data bthrough independent electrodes.